count source_label source_id relationship target_label target_id entity_type solr_id publication_id sentences 32 MESH:D002164 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype bdc62384-bc03-11e5-9b9d-001a4ae51247 10.1016/j.fct.2008.06.054 Camphor was determined to increase the content of glucuronide in the urine. 16 UNIPROT:P15104 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 56031038-cb8d-11e5-8106-001a4ae51247 11115509 The results of a screen of the effects of a broad range of GS conjugates demonstrated that at a sub-Kmconcentration of [3H]E217βG (100 μm) DNP-GS was the only GS conjugate that stimulated glucuronide uptake (TableI). 12 MESH:D005905 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c74ccde6-bc2f-11e5-8d2d-001a4ae51247 10.1016/S0014-5793(03)01064-0 In the presence of DNB-GS as stimulatory agent, theK1/2value for glucuronide uptake inhibition by glibenclamide was significantly lower (12±5 μM;Fig. 1) suggesting that the rise in glucuronide uptake activity induced by glutathione conjugates may also modulate the sensitivity of this transport mechanism towards glibenclamide.|||Glucuronide uptake was reduced to 13% of the control value by 150 μM glibenclamide.|||Glibenclamide selectively inhibited the uptake of glucuronide conjugates and other organic anions but not that of glutathione conjugates in barley mesophyll andArabidopsiscell culture vacuoles.|||Glibenclamide inhibits glucuronide but not glutathione transport activities in barley mesophyll vacuoles The sulfonylurea glibenclamide strongly inhibited the ATP-dependent transport of [3H]E217G into barley vacuoles (Table 1). 12 MESH:D011339 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype f3aa3364-3776-11e8-87fd-001a4a160176 15781124 In another study, probenecid reduced the urinary excretion of temazepam glucuronide, although it was not possible to determine whether the interaction was due to inhibition of UGT enzyme or inhibition of renal secretion (Brockmeyer et al., 1990).|||The inhibitory effect of probenecid on AZT elimination has been suggested to be therapeutically useful.Kornhauser et al. (1989)andde Miranda et al. (1989)demonstrated that probenecid decreased the CLRof the glucuronide and increased the AUC of the glucuronide (de Miranda et al., 1989).|||Probenecid, at steady-state levels, decreases the ClRof indomethacin glucuronide, but it had no effect on thet1/2of the parent compound or serum levels of indomethacin glucuronide (Baber et al., 1978). 11 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:O75762 Protein 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 Ibuprofen-acyl glucuronide also selectively attenuated the TRPA1-dependent component of the proalgesic responses evokedin vivoby formalin or carrageenan, thus underlying the hypothesis that TRPA1 targeting by ibuprofen-acyl glucuronide contributes to both analgesic and anti-inflammatory effects of ibuprofen.|||Further studies are needed to establish whether TRPA1 antagonism by ibuprofen-acyl glucuronide contributes to the therapeutic effect of ibuprofen in pain and inflammation in humans, and whether ibuprofen-acyl glucuronide may have an efficacy and safety profile different from its parent drug.|||The observation that both systemic ibuprofen and ibuprofen-acyl glucuronide completely inhibited PGE2generation evoked by carrageen, indicates that the metabolite maintains the COX inhibitory activity of the parent drug, and justify the complete attenuation of carrageenan-evoked allodynia by ibuprofen-acyl glucuronide which may simultaneously inhibit COXs and TRPA1.|||Thus, ibuprofen-acyl glucuronide was able to selectively block the human and rodent TRPA1 channel.|||Finally, ibuprofen-acyl glucuronide attenuated carrageenan-evoked PGE2release in TRPA1 deleted (Trpa1−/−) mice (Fig. 5I).|||Therefore, we investigated whether ibuprofen-acyl glucuronide antagonizes TRPA1 and,viathis mechanism, contributes to the analgesic and anti-inflammatory actions of ibuprofen.|||This conclusion derives, primarily, from thein vitropharmacological profile of ibuprofen-acyl glucuronide, which, unlike ibuprofen, selectively inhibits the recombinant and native human TRPA1 and the native rodent channel in nociceptors.|||The ability of ibuprofen-acyl glucuronide to inhibit TRPA1 by binding key cysteine and lysine residues was further proved by the study of the mutated human TRPA1 (3C/K-Q hTRPA1), which lacks the cysteine and lysine residues, required for channel activation by reactive agonists, and which responds to menthol [9,11,12].|||Ibuprofen-acyl glucuronide selectively inhibits TRPA1-mediated nocifensor responses Next, we speculated that ibuprofen-acyl glucuronide producesin vivoantinociceptive effectsviaTRPA1 antagonism.|||Thus, the ability of ibuprofen-acyl glucuronide to inhibit TRPA1 depends on the cysteine/lysine residues required for channel activation by electrophilic/reactive agonists.|||We also wondered whether ibuprofen-acyl glucuronide ability to inhibit TRPA1 may exert anti-inflammatory activity in an ibuprofen-independent manner. 10 CHEBI:89981 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 850deb34-bc4a-11e5-9b9d-001a4ae51247 10.1016/S0014-2999(01)01470-4 Endotoxin significantly decreased the systemic clearance, biliary clearance and renal clearance ofp-nitrophenyl glucuronide by approximately 30%, 40% and 30%, respectively.|||On the other hand, endotoxin significantly increased the area under plasma concentration–time curve (2.0 to 3.5 μg h/ml) and decreased the biliary clearance of sparfloxacin glucuronide (1.6 to 0.7 l/h/kg).|||Endotoxin was also shown to decrease the biliary clearance of sparfloxacin glucuronide. 8 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q16769 Protein 3c2db5fc-004c-11f0-9e78-0050569a1f61 10.1016/j.foodchem.2024.141784 After the treatments with crude and salt-stir fried EC extracts, the indoxyl glucuronide levels restored nearly to the control level, among which salt-stir fried EC extracts displayed the optimal regulatory function. 8 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002277 Phenotype 0d88c9e6-3419-11e8-a34b-001a4a160175 15279879 Early works have shown that 13-cis-retinoic acid (RA) reduced both incidence and severity of BBN induced urinary bladder carcinomas in C57 BL mice (our B6)[34]. 8 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002779 Phenotype 4eac3a4e-cd04-11e5-b6ad-001a4ae51246 8621644 Inhibition of [3H]E217βG Transport by Various Steroid Glucuronides and Bile Salt Derivatives E217βG and other steroid D-ring glucuronide conjugates have been shown to inhibit bile flow and to cause a reversible type of cholestasis(31,32,33).|||E217βG and other steroid D-ring glucuronide conjugates have been shown to inhibit bile flow and to cause a reversible type of cholestasis(31,32,33). 8 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009020 Phenotype 79b0d934-bc47-11e5-9b9d-001a4ae51247 10.1016/j.aca.2006.04.042 Morphine glucuronide elutes first due to its high polarity and on terms of fragmentation an initial MS/MS step produces just the morphine [M+H]+ion, loosing the glucurunic acid part.|||Morphine Morphine glucuronide elutes first due to its high polarity and on terms of fragmentation an initial MS/MS step produces just the morphine [M+H]+ion, loosing the glucurunic acid part. 8 MESH:D015215 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype f3aa3364-3776-11e8-87fd-001a4a160176 15781124 All of these studies involved patients infected with human immunodeficiency virus (HIV) or those diagnosed with AIDS.Lee et al. (1996)reported that the coadministration of atovaquone with AZT decreased theCmaxof the glucuronide and the ratio of the glucuronide to the parent compound. 8 UNIPROT:P06133 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 74cf99c4-352a-11e8-b868-001a4a160176 25760529 UGT2B4: UGT2B4 contributes to the detoxification of bile acids such as HDCA and HCA by glucuronidation, allowing their glucuronide efflux from hepatocytes via transporters such as multidrug resistance-associated protein (MRP) 2 or MRP3[156,157]. 8 MESH:D005047 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 82f4d89c-cb29-11e5-8189-001a4ae51246 11581266 Synthesis of [3H]Glucuronosyl Etoposide Synthesis of etoposide glucuronide was as described by others (6,30) with several minor modifications. 8 MESH:D003474 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype e3830a0a-bbff-11e5-8abe-001a4ae51246 PMC2034522 Results show curcumin inhibited in-vivo glucuronidation causing both a significant increase in free bilirubin in portal blood and a reduction in tissue bilirubin–glucuronide. 8 PF:PF02829 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 82f4d89c-cb29-11e5-8189-001a4ae51246 11581266 Synthesis of [3H]Glucuronosyl Etoposide Synthesis of etoposide glucuronide was as described by others (6,30) with several minor modifications. 8 MESH:D053626 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype f3aa3364-3776-11e8-87fd-001a4a160176 15781124 All of these studies involved patients infected with human immunodeficiency virus (HIV) or those diagnosed with AIDS.Lee et al. (1996)reported that the coadministration of atovaquone with AZT decreased theCmaxof the glucuronide and the ratio of the glucuronide to the parent compound. 8 MESH:D011794 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 3f86edce-ca5d-11e5-9088-001a4ae51247 12936951 Intragastric quercetin (10 or 50 mg/kg) raised plasma concentrations of quercetin glucuronide and/or sulfate conjugates and the plasma was more resistant to copper sulfate–induced lipid peroxidation than the control plasma on the basis of the accumulation of cholesterol ester hydroperoxides and the consumption of α-tocopherol (50).|||Quercetin as in vivo antioxidant Intragastric quercetin (10 or 50 mg/kg) raised plasma concentrations of quercetin glucuronide and/or sulfate conjugates and the plasma was more resistant to copper sulfate–induced lipid peroxidation than the control plasma on the basis of the accumulation of cholesterol ester hydroperoxides and the consumption of α-tocopherol (50). 6 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10635 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 Sertraline carbamoyl glucuronide caused strong time-dependent inhibition (97–100 %) of CYP2A6, CYP2C19, CYP2D6 and CYP2J2 at 500 µM, but the inhibition was not NADPH-dependent.|||Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 6 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P33261 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 Sertraline carbamoyl glucuronide caused strong time-dependent inhibition (97–100 %) of CYP2A6, CYP2C19, CYP2D6 and CYP2J2 at 500 µM, but the inhibition was not NADPH-dependent.|||A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 6 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P11509 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 Sertraline carbamoyl glucuronide caused strong time-dependent inhibition (97–100 %) of CYP2A6, CYP2C19, CYP2D6 and CYP2J2 at 500 µM, but the inhibition was not NADPH-dependent.|||A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 6 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P51589 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 Sertraline carbamoyl glucuronide caused strong time-dependent inhibition (97–100 %) of CYP2A6, CYP2C19, CYP2D6 and CYP2J2 at 500 µM, but the inhibition was not NADPH-dependent.|||Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:A8MT33 Protein 00c8740a-376f-11e8-8636-001a4a160175 16472997 Phenobarbital glucuronide is excreted into bile by Mrp2 and has been shown in vitro to inhibit Mrp2 function, so phenobarbital glucuronide may act as a competitive Mrp2 inhibitor (Patel et al., 2003; Xiong et al., 2002b). 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:O00206 Protein a76f19b4-ee3b-11e5-9b35-001a4ae51246 PMC4275344 As the focus of this paper is the glucuronide metabolite activation of TLR4, these effects remain for further investigation. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P19320 Protein 304258be-009d-11f0-9f22-0050569a1f61 10.1016/j.freeradbiomed.2024.10.289 3,4-Dihydroxybenzoic acid7and four phase-2 glucuronide and sulfate conjugates decreased the secretion of VCAM-1 and/or IL-6 proteins in vascular endothelial cells challenged with CD40L or oxidized LDL at a concentration of 0.1 μmol/L [50]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:17243 Chemical 1f44f966-3513-11e8-9fbf-001a4a160176 26815919 For example, metabolism of DEHP involves very rapid hydrolysis to MEHP catalyzed by nonspecific lipases and formation of a glucuronide conjugate[33]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 demethylatesProtein CHEBI:28870 Chemical e2650f22-3549-11e8-9192-001a4a160175 18164892 For example, monohydroxy-hexamethoxyflavone glucuronide (m/z595) detected in plasma was either from heptamethoxyflavone as its glucuronide of demethylated product or from monohydroxy-hexamethoxyflavone as it glucuronide. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:327119 Chemical 9aac4eb8-bbfa-11e5-8abe-001a4ae51246 10.1016/S1388-1981(03)00068-4 2-Azetidinone cholesterol absorption inhibitors such as S 6503(Fig. 1E), ezetimibe or ezetimibe glucuronide had no influence on the labeling pattern of rabbit small intestinal brush border membrane vesicles with [3H]photocholesterol(Fig. 3a), indicating that cholesterol absorption inhibitors do not compete with (photo)cholesterol for binding to the 80-kDa cholesterol-binding protein. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:35701 Chemical 78cf887c-3543-11e8-8636-001a4a160175 16842856 2, addition of a glucuronide to the carboxylic acid functional group produces an acyl (or ester-linked) glucuronide that is an electrophilic metabolite with sufficient reactivity to adduct proteins and other biomolecules. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases CHEBI:10136 Chemical 67a52784-3758-11e8-8636-001a4a160175 27700987 Based on the concentration-time curves the AUCs were calculated for [6]-gingerol glucuronide at 147μmol/L*h and for [8]-gingerol glucuronide at 1.5μmol/L*h. Further, the cumulative amounts of each gingerol glucuronide excreted in 24-h urine enabled calculation of the recovered amount of the gingerol dose administered with the tea. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:3558 Chemical 54ff0884-3906-11e8-9192-001a4a160175 28109684 Shitara et al. have investigated the mechanisms of this DDI and found that the glucuronide of gemfibrozil (gemfibrozil 1-O-β-glucuronide) inhibited the CYP2C8-mediated hepatic metabolism of cerivastatin to increase its systemic exposure[12]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases CHEBI:8613 Chemical 53dba90a-3544-11e8-9fbf-001a4a160176 16999974 Glucuronide hydrolysis prior to psilocin analysis was performed to increase the amount of detectable urinary psilocin using the method of Grieshaber et al.[19]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D044948 Phenotype 5057c1c4-bbfc-11e5-9b9d-001a4ae51247 PMC4428793 For all flavonols, decreases in the total amounts of metabolites were caused by lower amounts of both glucuronide and sulphate conjugates. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008283 Phenotype 21f2b36c-f1f7-11e5-9a27-001a4ae51246 16778789 The retinoid with the most potent effects on the proliferation of sebocytes, 13-cis-retinoic acid (13-cis-RA), significantly suppressed SZ95 proliferation at 10−5and 10−6M(P<0.001), but not at 10−7M(Figure 3c). 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008283 Phenotype 2d312520-3aab-11e8-a34b-001a4a160175 27771500 In contrast to BPAF, BPAF glucuronide did not induce expression of estrogen-responsive genes in the T47D cell line, and did not stimulate proliferation of MCF7 cells. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008283 Phenotype 5da3278a-f0da-11ee-b346-0050569a791b 10.1016/S0302-2838(03)00191-X 13-cis-retinoic acid (CRA), a vitamin A derivative, can markedly upregulate the differentiation and proliferation of normal and neoplastic cells and synergistic effects of IFN and CRA have been described[30]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002784 Phenotype 9aac4eb8-bbfa-11e5-8abe-001a4ae51246 10.1016/S1388-1981(03)00068-4 2-Azetidinone cholesterol absorption inhibitors such as S 6503(Fig. 1E), ezetimibe or ezetimibe glucuronide had no influence on the labeling pattern of rabbit small intestinal brush border membrane vesicles with [3H]photocholesterol(Fig. 3a), indicating that cholesterol absorption inhibitors do not compete with (photo)cholesterol for binding to the 80-kDa cholesterol-binding protein. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0045444 Phenotype a9f92ece-3513-11e8-b868-001a4a160176 PMC6415542 However, recentin-vitrofindings suggested that the glucuronide form of BPA was able to induce adipocyte differentiation in human and 3T3L1 murine preadipocytes (Boucher et al., 2015). 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D001749 Phenotype 0caaee0a-338d-11e8-8636-001a4a160175 16413099 The vitamin A analog, 13-cis-retinoic acid, has been shown to reduce the incidence, number, and grade of bladder tumors induced by exposure to the carcinogen BBN[64]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008152 Phenotype 54ff0884-3906-11e8-9192-001a4a160175 28109684 Shitara et al. have investigated the mechanisms of this DDI and found that the glucuronide of gemfibrozil (gemfibrozil 1-O-β-glucuronide) inhibited the CYP2C8-mediated hepatic metabolism of cerivastatin to increase its systemic exposure[12]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype 5da3278a-f0da-11ee-b346-0050569a791b 10.1016/S0302-2838(03)00191-X 13-cis-retinoic acid (CRA), a vitamin A derivative, can markedly upregulate the differentiation and proliferation of normal and neoplastic cells and synergistic effects of IFN and CRA have been described[30]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D051379 Phenotype 0d88c9e6-3419-11e8-a34b-001a4a160175 15279879 Early works have shown that 13-cis-retinoic acid (RA) reduced both incidence and severity of BBN induced urinary bladder carcinomas in C57 BL mice (our B6)[34]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009765 Phenotype d60e5bbc-351b-11e8-bf76-001a4a160175 28806569 The production of both 2,8-dihydroxyquinolin and its glucuronide was significantly elevated in mouse urine by the antioxidant drug tempol[16], which can protect against high-fat diet induced obesity through regulating the composition of gut micriobiota[27]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002085 Phenotype 0d88c9e6-3419-11e8-a34b-001a4a160175 15279879 Alteration of embryonic biochemical systems Early works have shown that 13-cis-retinoic acid (RA) reduced both incidence and severity of BBN induced urinary bladder carcinomas in C57 BL mice (our B6)[34]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates FPLX:Interferon ProteinFamily 5da3278a-f0da-11ee-b346-0050569a791b 10.1016/S0302-2838(03)00191-X 13-cis-retinoic acid (CRA), a vitamin A derivative, can markedly upregulate the differentiation and proliferation of normal and neoplastic cells and synergistic effects of IFN and CRA have been described[30]. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:PKC ProteinFamily 14edfcd2-f295-11e5-95fd-001a4ae51246 15569301 Interestingly, a recent in vitro study showed that pharmacologic concentrations of tRA, 9cRA, 4-OH-tRA, and tRA glucuronide directly bind PKCα, hampering binding of phosphatidylserine to PKCα, and preventing PKCα activation44. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D004249 Phenotype 12aefa38-f11b-11ee-b346-0050569a791b 10.1016/S0009-2797(02)00253-3 Since these organs are exposed to high biliary concentrations of glucuronides[1], these observations may raise the possibility that glucuronide-induced DNA damage in these tissues participates in the tumorigenic process.|||Thus, the possibility that acyl glucuronide-mediated DNA damage and aglycone-mediated cell and peroxisome proliferation co-operate during the neoplastic process, could be deserving of future attention. 4 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:29108 Chemical 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 The calcium responses evoked by AITC in NHBE cells, which constitutively express TRPA1 [27], were attenuated in a concentration-dependent manner by ibuprofen-acyl glucuronide [IC50, 20 (CI, 13–40) μM] and HC-030031 [IC50,10 (CI, 8–12) μM] (Fig. 7A–C).|||Ibuprofen-acyl glucuronide reduced calcium responses evoked by additional reactive TRPA1 agonists, such as acrolein or hydrogen peroxide (H2O2) (Fig. 1D), but did not affect the responses by non-reactive agonists, icilin and zinc chloride (ZnCl2) (Fig. 1D), which do not act by binding key cysteine residues of TRPA1 [51,52].|||Ibuprofen-acyl glucuronide also inhibited the AITC-evoked calcium response in IMR90 cells, a cell line where TRPA1 was originally cloned [53], (Fig. 2A), and which constitutively expresses the channel.|||Ibuprofen-acyl glucuronide [IC50s, 60 (CI, 45–88) μM] and HC-030031 [IC50s, 3 (CI, 2–6) μM] reduced AITC-evoked calcium responses (Fig. 2B,C). 4 CHEBI:16002 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 991147c8-0cd8-11f0-b759-0050569a791b 10.1016/S1040-8428(99)00076-1 Calcium glucarate inhibits glucronidase, thereby increasing urinary glucuronide excretion such as estradiol and 17 ketosteroids. 4 MESH:D005978 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype e4766f54-3391-11e8-8f56-001a4a160175 11557126 However, given what we now know about the substrate specificity of MRP1, in particular, the ability of GSH to stimulate the transport of sulphate and glucuronide conjugates (Leslie et al., 2001b; Qian et al., 2001; Sakamoto et al., 1999) and the identification of specific amino acid residues (e.g. 4 MESH:D005978 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c74ccde6-bc2f-11e5-8d2d-001a4ae51247 10.1016/S0014-5793(03)01064-0 In the presence of DNB-GS as stimulatory agent, theK1/2value for glucuronide uptake inhibition by glibenclamide was significantly lower (12±5 μM;Fig. 1) suggesting that the rise in glucuronide uptake activity induced by glutathione conjugates may also modulate the sensitivity of this transport mechanism towards glibenclamide. 4 PF:PF00702 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily b7516e5a-0d39-11f0-aa93-0050569a1f61 10.1016/S0031-9422(98)00454-3 Glycyrrhizinic acid hydrolase produced byAspergillus nigerselectively hydrolyzes the 3-O-β-d-glucuronide linkages of GOTCAB with free 4-OH and 6-COOH in the glucuronide moiety to give 3-oligosaccharides and 28-prosapogenins[113–115]. 4 UNIPROT:P35503 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9a9f9806-3913-11e8-bf76-001a4a160175 24296138 In comparison, both UGT2B7 and UGT1A3 produced high levels of steviol glucuronide at a high steviol concentration (20μM), with minimal contribution from UGT2B4 and UGT2B17. 4 MESH:D006859 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 7aa4913a-3749-11e8-a51f-001a4a160176 26162556 In HMBC spectrum, the proton signal atδ4.68 (inM7)/4.48 (inM9) of glucuronide moiety were correlative with the carbon signal atδ70.9/69.2 (C-7), indicating that the glucuronosyl moiety ofM7andM9were linked to C-7 (Fig. 3). 4 MESH:D002118 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 991147c8-0cd8-11f0-b759-0050569a791b 10.1016/S1040-8428(99)00076-1 Calcium glucarate inhibits glucronidase, thereby increasing urinary glucuronide excretion such as estradiol and 17 ketosteroids. 4 MESH:D011339 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 8642aba6-354d-11e8-a34b-001a4a160175 15325035 Horikawa et al. reported that the coadministration of probenecid reduced the biliary excretion of CPT-11, an active metabolite (SN-38) and its glucuronide by half with a concomitant increase in their plasma concentration. 4 MESH:D011339 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype f3aa3364-3776-11e8-87fd-001a4a160176 15781124 The inhibitory effect of probenecid on AZT elimination has been suggested to be therapeutically useful.Kornhauser et al. (1989)andde Miranda et al. (1989)demonstrated that probenecid decreased the CLRof the glucuronide and increased the AUC of the glucuronide (de Miranda et al., 1989). 4 CHEBI:28870 demethylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical e2650f22-3549-11e8-9192-001a4a160175 18164892 For example, monohydroxy-hexamethoxyflavone glucuronide (m/z595) detected in plasma was either from heptamethoxyflavone as its glucuronide of demethylated product or from monohydroxy-hexamethoxyflavone as it glucuronide. 4 MESH:D012965 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype b4aee7ee-0033-11f0-9c09-0050569a791b 10.1016/j.ijbiomac.2024.139095 The absorption peaks near 1610 cm−1and 1411 cm−1are an asymmetric vibration peak and a symmetric vibration peak of the CO double bond, respectively, indicating that CVP-n contains carboxyl groups, and as the concentration of NaCl increased, the content of glucuronide in CVP-n increases. 4 CHEBI:89981 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 850deb34-bc4a-11e5-9b9d-001a4ae51247 10.1016/S0014-2999(01)01470-4 1, endotoxin dramatically delayed the disappearance of sparfloxacin from plasma and significantly increased the plasma concentrations of sparfloxacin glucuronide compared to the control rats.Table 1shows the corresponding pharmacokinetic parameters of sparfloxacin and the glucuronide. 4 MESH:D003902 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 00c8740a-376f-11e8-8636-001a4a160175 16472997 This transport process is disrupted in vitro in isolated microsomal incubations; thus, low detergent or pore-forming peptide (alamethacin) concentrations are necessary to allow UDP-GA to enter and glucuronide conjugates to exit the microsomal lumen in order to approach glucuronidation rates comparable to intact hepatocytes (Dutton, 1980; Fisher et al., 2001; Soars et al., 2003). 4 MESH:D005399 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 398c37ae-bbde-11e5-9b9d-001a4ae51247 PMC2268215 The only other fish species for which phase II metabolism of MXC has been reported, the rainbow trout, produced glucuronide conjugates of both OH-MXC and HPTE in precision-cut liver slices incubated at 15°C, and these were the major metabolites found (Ohyama et al., 2004). 4 UNIPROT:P16662 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9a9f9806-3913-11e8-bf76-001a4a160175 24296138 In comparison, both UGT2B7 and UGT1A3 produced high levels of steviol glucuronide at a high steviol concentration (20μM), with minimal contribution from UGT2B4 and UGT2B17. 4 UNIPROT:O15438 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 27af99ca-341a-11e8-a51f-001a4a160176 17681807 MRP3 mediates the transport of glucuronide conjugates, taurocholate, glycocholate, and methotrexate. 4 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 353d568c-3a81-11e8-9fbf-001a4a160176 26708112 Various isoforms of UGT could act on the EFV metabolites to produce the glucuronide forms, including UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10 and 2B7[81,82]. 4 MESH:D009288 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype f3aa3364-3776-11e8-87fd-001a4a160176 15781124 In contrast, the coadministration of indomethacin and naproxen did not alter the pharmacokinetics of zidovudine, although naproxen did decrease the AUC of the glucuronide (Barry et al., 1993). 4 MESH:D019695 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype b7516e5a-0d39-11f0-aa93-0050569a1f61 10.1016/S0031-9422(98)00454-3 Glycyrrhizinic acid hydrolase produced byAspergillus nigerselectively hydrolyzes the 3-O-β-d-glucuronide linkages of GOTCAB with free 4-OH and 6-COOH in the glucuronide moiety to give 3-oligosaccharides and 28-prosapogenins[113–115]. 4 CHEBI:39867 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical d3fbfab0-3745-11e8-a34b-001a4a160175 26674479 The proportion of free VPA increases as the total molecular concentration increases.5VPA undergoes extensive hepatic metabolism through 4 distinct pathways: glucuronide conjugation (30%–50%), mitochondrial β-oxidation (40%), and ω1 and ω2 oxidation (5%–20%, combined). 4 CHEBI:39867 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical f3aa3364-3776-11e8-87fd-001a4a160176 15781124 Valproic acid decreased the AUC andCmaxof AZT glucuronide (Lertora et al., 1994) and this was accompanied by decreases in the CL/F and volume of distribution (Vd), and increase in the AUC of the parent compound. 4 PF:PF08947 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 2d312520-3aab-11e8-a34b-001a4a160175 27771500 BPS metabolism leads mainly to BPS glucuronide (Fig. 7,40) (Skledar et al., 2016). 4 CHEBI:36796 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1cf5c49e-bc1e-11e5-8abe-001a4ae51246 10.1016/j.jchromb.2007.02.025 Thus, liver slice incubations with 4-, 5-, and 6-hydroxy duloxetine which produced the desired glucuronide conjugates were utilized during method development. 4 CHEBI:7603 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 4895c358-390b-11e8-9192-001a4a160175 25477003 Application of nobilin as plant extract caused a significant reduction of the apical efflux rate constant of glucuronide, cysteine conjugate, and glutathione conjugate of 2.7-, 2.6-, and 6-fold, respectively. 4 MESH:D018120 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype aeab2cd4-3954-11e8-a34b-001a4a160175 10428146 Finasteride produced a statistically significant increase in T at 6 months (0.7 ± 0.1 ng/mL) and at 12 months (0.8 ± 0.2 ng/mL) and an equally significant reduction in 3α-androstanediol glucuronide at 6 months (2.4 ± 0.8 ng/mL) and at 12 months (1.8 ± 0.4 ng/mL).|||Our hormone results demonstrated that finasteride, a 5α-reductase type 2 selective inhibitor, increased serum levels of T by 40% at 6 months and by 60% at 12 months, and reduced 3α-androstanediol glucuronide by 59.3% at 6 months and by 69.5% at 12 months. 4 MESH:D014147 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype b726961e-bbd9-11e5-956b-001a4ae51247 10.1016/j.jpain.2003.09.007 In both normal rats and rats with renal insufficiency tramadol at clinical doses had little effect on renal blood flow and produced an increase in norepinephrine blood levels.109 Tramadol administration has been claimed to be dangerous for patients with renal impairment.104A case of respiratory depression after administration of oral tramadol has been reported in a patient with impaired renal function.12 Butorphanol Butarphanol is metabolized in hydroxybutorphanol, norbutorphanol, and glucuronide conjugates.|||In both normal rats and rats with renal insufficiency tramadol at clinical doses had little effect on renal blood flow and produced an increase in norepinephrine blood levels.109 Tramadol administration has been claimed to be dangerous for patients with renal impairment.104A case of respiratory depression after administration of oral tramadol has been reported in a patient with impaired renal function.12 Butarphanol is metabolized in hydroxybutorphanol, norbutorphanol, and glucuronide conjugates. 3 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:18135 Chemical d2e32a00-c8ec-11e5-b79b-001a4ae51246 18372400 "The three metabolites detected were the glucuronide conjugate of lasofoxifene (M7), its hydroxylated metabolite (M9), and a methylated catechol (M17)." 3 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009447 Phenotype 959dbbb0-ac41-11ee-a19b-0050569a791b PMC7434894 Lastly, our results identify critical intracellular signalling pathways in neuroblastoma cells that are inhibited or activated by regorafenib, 13-cis-retinoic acid and the combination of regorafenib with 13-cis-retinoic acid, and identify additional targets that may represent mechanisms of treatment resistance.|||Retinoids are vitamin A analogues that induce tumour cell differentiation,63and 13-cis-retinoic acid treatment of neuroblastoma cells in vitro both induces neuroblastoma cell differentiation and reduces neuroblastoma cell proliferation.64,65–6613-cis-retinoic acid is also currently a component of standard maintenance therapy in the most common protocols utilised for the treatment of children with high-risk neuroblastoma.35Morphologic neuroblastoma cell differentiation induced by retinoids in vitro occurs over the course of 7–10 days, but the pathways activated prior to the morphologic differentiation are poorly understood. 3 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein 848fbaf6-ca01-11e5-b88f-001a4ae51247 16299161 "As a metabolism-dependent inhibitor, gemfibrozil glucuronide inhibited CYP2C8 with roughly the same potency regardless of whether the concentration of human liver microsomes was 0.1 or 1.0 mg/ml.|||Furthermore, the potency with which gemfibrozil glucuronide inhibited CYP2C8 increased by an additional order of magnitude after a 30-min preincubation with NADPH-fortified human liver microsomes, as shown inFig.|||The mechanism by which gemfibrozil glucuronide inactivates CYP2C8 remains to be determined, but some mechanistic information is apparent from the results of the present study." 3 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P10632 Protein 848fbaf6-ca01-11e5-b88f-001a4ae51247 16299161 "Incubating these same samples with NADPH caused a further loss of CYP2C8 activity, presumably because of the metabolism-dependent inhibition of CYP2C8 by gemfibrozil glucuronide (Fig. 5).|||Accordingly, experiments were performed to determineKI(the concentration of gemfibrozil glucuronide supporting the half-maximal rate of CYP2C8 inactivation) andkinact(the first order rate constant for CYP2C8 inactivation).|||Accordingly, gemfibrozil was incubated with human liver microsomes in the presence of UDP-glucuronic acid (to support the formation of gemfibrozil glucuronide) and then in the presence of NADPH (to support the metabolism-dependent inactivation of CYP2C8 by gemfibrozil glucuronide)." 3 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0019233 Phenotype 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 Local injection of ibuprofen-acyl glucuronide in the mouse hind paw prevented acute nociception elicited by local administration of the reactive TRPA1 agonists, AITC and acrolein, but was ineffective against TRPV1 or TRPV4 agonists, indicating selectivity.|||Computational results with the mutated channel confirm that the inhibitory activity of ibuprofen-acyl glucuronide should be ascribed to its interaction with one of the mutated residues.In vivoresults that ibuprofen-acyl glucuronide attenuated nociception evoked by reactive TRPA1 agonists, but not those produced by non-reactive agonists, such as icilin and zinc chloride, further supported thein vitrodata and simulation experiments, underlining that chemical reactivity is required for TRPA1 targeting by ibuprofen-acyl glucuronide.|||Ibuprofen-acyl glucuronide reduces TRPA1-dependent hyperalgesia and nociception in models of inflammatory pain We tested the ability of ibuprofen-acyl glucuronide to reduce mechanical allodynia evoked by intraplantar carrageenan injection in the mouse hind paw. 3 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a1612518-c7cb-11ee-9aaa-0050569a1f61 10.1016/j.pharmthera.2023.108459 It has been proposed that the minor decrease in mycophenolic acid exposure arises from increased MRP2-mediated biliary excretion of mycophenolic acid phenolic glucuronide (Brazeau et al., 2021;Naesens et al., 2006).|||It has been reported that tipranavir is an inhibitor of hepatocellular MRP2 activity in vitro (Holmstock et al., 2018), which could potentially lead to a decrease in the biliary excretion of dolutegravir glucuronide and the postulated enterohepatic recirculation of dolutegravir (Section 3.2.2).|||Although available evidence suggests that faecal excretion of dolutegravir and possibly enterohepatic recycling arises from MRP2-mediated canalicular efflux of the glucuronide conjugate (Section 3.2.2), concurrent induction of MRP3-mediated sinusoidal efflux of dolutegravir glucuronide by carbamazepine (Section 7.3.2) may modulate the extent of biliary excretion. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P01241 Protein c69eb3ae-bbe0-11e5-8abe-001a4ae51246 10.1016/j.metabol.2007.02.002 13-cis-Retinoic acid temporarily disrupted the interrelationship between several inflammatory parameters such as the association of ESR to ALT, GH to LDL-C, C3 to triglycerides, and haptoglobin to IL-6. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P20585 Protein 2c962c8c-3777-11e8-8f56-001a4a160175 15795089 Previous studies have shown that many, but not all, glucuronide conjugates can inhibit MRP1-mediated uptake of organic anions into inside-out membrane vesicles (Leslie et al., 2001; Loe et al., 1996a). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P00738 Protein c69eb3ae-bbe0-11e5-8abe-001a4ae51246 10.1016/j.metabol.2007.02.002 13-cis-Retinoic acid temporarily disrupted the interrelationship between several inflammatory parameters such as the association of ESR to ALT, GH to LDL-C, C3 to triglycerides, and haptoglobin to IL-6. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P05231 Protein c69eb3ae-bbe0-11e5-8abe-001a4ae51246 10.1016/j.metabol.2007.02.002 13-cis-Retinoic acid temporarily disrupted the interrelationship between several inflammatory parameters such as the association of ESR to ALT, GH to LDL-C, C3 to triglycerides, and haptoglobin to IL-6. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein dbde4c98-3758-11e8-8f56-001a4a160175 27457785 However, the mechanism of gemfibrozil-mediated DDI and clinical DDI data with cerivastatin have already found that gemfibrozil increased the plasma concentration of cerivastatin with the inhibition of CYP2C8 and OATP1B1 by gemfibrozil glucuronide (Backman et al., 2002;Shitara et al., 2004;Kudo et al., 2013). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y6L6 Protein dbde4c98-3758-11e8-8f56-001a4a160175 27457785 However, the mechanism of gemfibrozil-mediated DDI and clinical DDI data with cerivastatin have already found that gemfibrozil increased the plasma concentration of cerivastatin with the inhibition of CYP2C8 and OATP1B1 by gemfibrozil glucuronide (Backman et al., 2002;Shitara et al., 2004;Kudo et al., 2013). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P01375 Protein fedf3272-3c8a-11f0-b8fe-0050569a1f61 PMC8991978 In a previous study, the authors showed that a vanillic acid metabolite (vanillic acid glucuronide) significantly reduced the release of TNF-α in THP-1 human cells (di Gesso et al., 2015). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:P03126 Protein 10ae0cf0-bbd3-11e5-8abe-001a4ae51246 10.1016/S0304-3835(01)00864-3 For example, 13-cis-retinoic acid induces radiosensitization in cervical cancer cell lines, probably by inhibiting the expression of human papillomavirus E6 gene[27]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P55157 Protein 56fdf8e0-2c36-11f0-b759-0050569a791b 10.1016/S0024-3205(02)02107-0 The highly reactive acyl glucuronide (which will readily form its rearrangement isomers at physiological pH and temperature), and its preformed rearrangement isomers, inhibited the assembly of MTP into microtubules to comparable extents, whereas the parent drug had little effect. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q15848 Protein c69eb3ae-bbe0-11e5-8abe-001a4ae51246 10.1016/j.metabol.2007.02.002 Taken together, despite disturbances in lipid and glucose metabolism, 13-cis-retinoic acid increases serum adiponectin concentration. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:O60259 Protein 6f6f43ee-1bfa-11f0-b759-0050569a791b 10.1016/j.envres.2023.117903 Müller et al. (1998)showed that after oral administration of13C6-NP in volunteers, only 10% of the administered dose was excreted in the urine as parental NP or as NP produced by cleavage of glucuronide and sulfate splices, but it has analytical background contamination. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:17243 Chemical 4d0c84ba-bc1e-11e5-8abe-001a4ae51246 10.1016/j.jchromb.2012.09.030 Metabolism of DEHP involves very rapid hydrolysis to mono-(2-ethylhexyl)phthalate (MEHP) catalysed by unspecific lipases and formation of a glucuronide conjugate. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:28870 Chemical 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:24298 Chemical 98b7202a-3406-11e8-8f56-001a4a160175 PMC5884633 The main metabolites of hydroxytyrosol collected in the urine are conjugated glucuronide forms, which are produced by linking glucuronic acid to other substances via glycosidic bonds[65]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:134301 Chemical 55e45e7c-f588-11eb-8b14-001a4a160175 30870692 They were danshensu (M1), salvianolic acid B glucuronide (M9), methylated salvianolic acid A (M17), hydrolysate of salvianolic acid B (M20) and rosmarinic acid glucuronide (M21). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:47774 Chemical c69eb3ae-bbe0-11e5-8abe-001a4ae51246 10.1016/j.metabol.2007.02.002 13-cis-Retinoic acid temporarily disrupted the interrelationship between several inflammatory parameters such as the association of ESR to ALT, GH to LDL-C, C3 to triglycerides, and haptoglobin to IL-6. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D006984 Phenotype d3099eca-04d7-11f0-bb39-0050569a791b 10.1016/j.nano.2024.102763 Beyond this Quercetin has demonstrated potential advantages against various health concerns including select cancer types: osteoporosis, respiratory issues, aging, and cardiovascular diseases.23,24Numerous investigations have revealed that both quercetin and its glucuronide derivative, quercetin 3-O-b-D-glucuronide, suppress the hypertrophy, proliferation, and migration of cultured VSMCin vitroupon activation by serum or growth factors. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006810 Phenotype c07eb51c-c46b-11e5-91a7-001a4ae51247 25380805 "In contrast to all other compounds, which caused greater inhibition of the high-affinity microsomal UDP-GlcUA pathway compared with the low-affinity pathway, 4-MU glucuronide and zidovudine glucuronide caused equal or greater inhibition of the low-affinity pathway, implying that, for some glucuronide conjugates, this may be the preferable transport process." 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006810 Phenotype 4fdb0c8a-4e3a-11e6-8f02-001a4ae51247 10.1074/jbc.275.6.4507 In contrast, glucuronide conjugates with similar hydrophobic side chains showed no or little inhibitory effect on OAT4-mediated transport. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006810 Phenotype 7032b132-3406-11e8-a34b-001a4a160175 28890383 In conclusion, rhein acyl glucuronide could significantly decrease the transport of methotrexate by both hOAT1 and hOAT3. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D007975 Phenotype d3431280-bc4e-11e5-8abe-001a4ae51246 10.1016/j.prostaglandins.2006.09.010 Preparation of LTB4 glucuronide Two isomers of LTB4 glucuronides were synthesized by reacting LTB4 with a mixture of UDP-glucuronosyltransferase cofactors containing uridine 5′-diphosphoglucuronic acid (BD Biosciences, Woburn, MA, USA) in the presence of human liver microsomes (BD Biosciences) according to manufacturer's instruction. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D000075222 Phenotype 537068da-c46b-11e5-91a7-001a4ae51247 PMC4396182 Previous studies by Ward et al.[29]in a number of Caucasian patients in Australia indicated that the urinary 20-HETE glucuronide levels were elevated about 27% in patients with essential hypertension. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0007268 Phenotype e1ed6708-5c99-11e7-b441-001a4ae51247 PMC5192019 It was later shown that 13-cis-retinoic acid, the active ingredient in Accutane, is able to induce depression-related behaviors in adolescent male mice and that the drug can modulate serotonergic neurotransmission in vitro (O׳Reilly et al., 2007). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008283 Phenotype d3099eca-04d7-11f0-bb39-0050569a791b 10.1016/j.nano.2024.102763 Beyond this Quercetin has demonstrated potential advantages against various health concerns including select cancer types: osteoporosis, respiratory issues, aging, and cardiovascular diseases.23,24Numerous investigations have revealed that both quercetin and its glucuronide derivative, quercetin 3-O-b-D-glucuronide, suppress the hypertrophy, proliferation, and migration of cultured VSMCin vitroupon activation by serum or growth factors. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008283 Phenotype 81dbea0c-c473-11e5-9da3-001a4ae51247 25661160 As can be seen inTable 6, also the glucuronide concentrations found in blood inhibited cell proliferation in our in vitro experiments. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002784 Phenotype cd722974-c8e5-11e5-9624-001a4ae51246 17473178 It has been shown that both ezetimibe and its glucuronide metabolite inhibit cholesterol absorption but that the glucuronide derivative is more potent. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D010100 Phenotype 38106256-bc2e-11e5-9b9d-001a4ae51247 PMC1459539 To study this issue, an enzymatically stable glucuronide analogue was synthesized by replacing the phenolic oxygen with a methylene group. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006006 Phenotype 8a54205a-352d-11e8-87fd-001a4a160176 29021286 Urolithins C and D stimulated deoxy-D-glucose uptake and modulated glucose metabolism, urolithin B glucuronide modulated glucose metabolism, and urolithin A inhibited deoxy-D-glucose uptake and modulated glucose metabolism. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0098814 Phenotype bb06a276-340c-11e8-9192-001a4a160175 24657077 The glucuronide derivative was also shown to interfere with the generation/aggregation of amyloid peptides in primary cortical neuron cultures and to rescue basal synaptic transmission deficit and neuronal plasticity in hippocampal slices from a mouse model of Alzheimer’s disease[36]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D014415 Phenotype c261c9a4-4824-11f0-afc2-0050569a791b 10.1016/j.jff.2016.12.033 However, glucuronide metabolites of HTyr may protect renal cell membranes against lipid peroxidation induced by external injury with H2O2(Deiana et al., 2011) and may inhibit tunicamycin-induced endoplasmic reticulum stress in human hepatic HepG2 cells (Giordano, Dangles, Rakotomanomana, Baracchini, & Visioli, 2015). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D019821 Phenotype 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 The combined direct and time-dependent inhibitory effects of diclofenac and its glucuronide on hepatic and intestinal CYP3A led to a predicted 2.0- and 5.8-fold increase in the exposure of midazolam and simvastatin, respectively (Table 3). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0098754 Phenotype e7350498-1b48-11f0-b40b-0050569a1f61 10.1016/j.yrtph.2024.105642 Saturation or inhibition of the glucuronide pathway would decrease detoxification and increase the potential for the generation of a cytotoxic metabolite (quinone methide). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D012601 Phenotype 96dc049a-04f2-11f0-bd9d-0050569a1f61 10.1016/j.forc.2024.100602 Glucuronide hydrolysis is strongly recommended prior to urinalysis to increase the signal of scopolamine, norscopolamine (M-S10) and 2/4-hydroxyscopolamine (M-S9) due to the conversion of the glucuronide conjugates to the corresponding aglycone. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D008874 Phenotype 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 The combined direct and time-dependent inhibitory effects of diclofenac and its glucuronide on hepatic and intestinal CYP3A led to a predicted 2.0- and 5.8-fold increase in the exposure of midazolam and simvastatin, respectively (Table 3). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0007021 Phenotype 56fdf8e0-2c36-11f0-b759-0050569a791b 10.1016/S0024-3205(02)02107-0 We have previously demonstrated that incubation of the (very reactive) acyl glucuronide of zomepirac, and its acyl migration rearrangement isomers, caused inhibition of tubulin assembly into microtubules, and we ascribed this to the covalent modification of critical structural elements on tubulin[21]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008152 Phenotype eb241654-376e-11e8-8636-001a4a160175 16488580 This is due to inhibition of the microsomal metabolism by gemfibrozil glucuronide (Shitara et al., 2004b). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D008727 Phenotype 7032b132-3406-11e8-a34b-001a4a160175 28890383 In conclusion, rhein acyl glucuronide could significantly decrease the transport of methotrexate by both hOAT1 and hOAT3. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D017328 Phenotype 5a617c46-3904-11e8-a34b-001a4a160175 22153801 Of them, some significantly elevated metabolites within diabetic kidney, including hippurate, 2-phenylethanol glucuronide, 2, 8-dihydroxyquinoline-beta-d-glucuronide/3-indole carboxylic acid glucuronide, 6-hydroxy-5-methoxyindole glucuronide/5-hydroxy-6-methoxyindole glucuronide and N-acetyl glucosamine were reduced effectively, which suggested the potential mechanisms of fosinopril in treating DKD. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D051379 Phenotype 2bbc3a62-c8df-11e5-9cb8-001a4ae51247 16988054 Hepatic basolateral excretion of glucuronide conjugates was decreased markedly inAbcc3–/–mice but was largely unaffected inAbcc4–/–mice (Fig. 3;Table 2). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D051379 Phenotype e1ed6708-5c99-11e7-b441-001a4ae51247 PMC5192019 It was later shown that 13-cis-retinoic acid, the active ingredient in Accutane, is able to induce depression-related behaviors in adolescent male mice and that the drug can modulate serotonergic neurotransmission in vitro (O׳Reilly et al., 2007). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008219 Phenotype 27ca6934-bc40-11e5-8d2d-001a4ae51247 10.1016/S0891-5849(01)00704-3 The purpose of this study was to examine the comparative mechanisms by which the dietary form of the flavonoid epicatechin (major component of wine, tea, cocoa, etc.) and its predominant in vivo metabolite, epicatechin glucuronide, influence oxidative stress-induced cell death in two systems: human dermal fibroblasts and primary cortical neurons. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006954 Phenotype 052f592c-338d-11e8-8f56-001a4a160175 16412693 In addition, it has been reported that 13-cis-retinoic acid of oral administration reduced inflammation and collagenase production in the adjuvant arthritis model rat[4]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D000544 Phenotype 6652dd68-3758-11e8-a51f-001a4a160176 27705748 Quercetin 3-O- glucuronide, a constituent of fruits and leaves of CM, isolated from red wine, generated fromVitis vinifera, showed neuroprotective effect by reducing the generation of β-amyloid (Aβ) peptides by primary neuron cultures in Tg2576AD mouse model and thus may be effective in prevention of Alzheimer's disease (AD) and other neurodegenerative disorders (Ho et al., 2013). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002277 Phenotype f994081e-bc4d-11e5-8abe-001a4ae51246 10.1016/j.cdp.2004.02.002 13-cis-Retinoic acid has been shown to prevent lung carcinomas in second-primary-tumor-prevention trials in human[43]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D000082 Phenotype 855de198-5c49-11e7-b441-001a4ae51247 PMC5113979 Acetaminophen (N-acetyl-p-aminophenol) is eliminated majorly by conjugation with glucuronide or sulfate in hepatocytes at therapeutic dosages. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0070508 Phenotype 2a1f9848-bc0a-11e5-8abe-001a4ae51246 PMC3216277 Studies with [125I]-labeled ezetimibe glucuronide and [14C]-labeled cholesterol have found that the glucuronide could block the cholesterol uptake into the enterocytes [2] because it is often detected in the brush border membrane, a site predominantly associated with cholesterol uptake and transepithelial transport. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits PF:PF01752 ProteinFamily 052f592c-338d-11e8-8f56-001a4a160175 16412693 In addition, it has been reported that 13-cis-retinoic acid of oral administration reduced inflammation and collagenase production in the adjuvant arthritis model rat[4]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates FPLX:RAR ProteinFamily b642a132-2c51-11f0-b759-0050569a791b 10.1016/S1040-8428(01)00190-1 High-dose 13-cis-retinoic acid treatment upregulated RARβ in these patients[13]. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits PF:PF06745 ProteinFamily 06e79b20-5c34-11e7-8c5f-001a4ae51246 PMC5286421 In accordance with the substrate accumulation assays carried out in live cells (Fig. 1), retinyl-acetate hampered the substrate-stimulated ATPase activity of Pgp and ABCG2 (Fig. 2c,f, brown symbols), while retinol and 13-cis-retinoic acid inhibited both the basal- and the substrate-stimulated ATPase activity of either transporters (Fig. 2a,b,d,e). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 phosphorylatesProtein FPLX:AKT ProteinFamily 3b853e6e-ca5e-11e5-8050-001a4ae51246 12826665 This was further highlighted by the fact that the glucuronide of quercetin, too polar to enter cells, expressed no significant toxicity and no ability to inhibit the phosphorylation of Akt/PKB. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:AKT ProteinFamily 4adef44a-391a-11e8-87fd-001a4a160176 21856292 Moreover, considering the limited oral bioavailability of quercetin and its rapid metabolism in cells, the report that itsO-methylated and glucuronide metabolites were able to inhibit the AKT/PKB and ERK1/2 pathways and, thus, induce apoptosis[63]was particularly interesting. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 dephosphorylatesProtein FPLX:AKT ProteinFamily 3b853e6e-ca5e-11e5-8050-001a4ae51246 12826665 This was further highlighted by the fact that the glucuronide of quercetin, too polar to enter cells, expressed no significant toxicity and no ability to inhibit the phosphorylation of Akt/PKB. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:A8MT33 Protein 2ae57bea-c8e8-11e5-9624-001a4ae51246 17332143 "Glucuronide conjugates of DPC 333 most likely inhibited Mrp2 rather than direct inhibition by the parent compound itself.|||DPC 333 almost completely blocked the biliary excretion of MTX in isolated perfused rat livers, likely due to inhibition of Mrp2 by the glucuronide conjugates of DPC 333." 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P20813 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:O95139 Protein 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 The intraplantar (20 μl/paw) administration of ibuprofen-acyl glucuronide or HC-030031 dose-dependently reduced [ID50of 4 (CI, 2–9) nmol, and ID50, 8 (CI, 3–23) nmol, respectively] the acute nociceptive response evoked by the injection of AITC (intraplantar).|||The systemic (intraperitoneal) administration of HC-030031, ibuprofen-acyl glucuronide and ibuprofen dose-dependently [ID50s7 (CI, 4–14) mg/kg, 10 (CI, 4–20) mg/kg and ID50s27 (CI, 8–90) mg/kg, respectively] reduced the nociceptive responses to AITC (intraplantar) (Fig. 4E). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P11712 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q3KNS1 Protein b7915338-ef45-11e5-9b35-001a4ae51246 22329675 Interestingly, darexaban and darexaban glucuronide increased PTR even when the degree of FXa inhibition was relatively low.|||Furthermore, darexaban and its human metabolite darexaban glucuronide produced higher PTR values than rivaroxaban or apixaban, regardless of the thromboplastin reagent used. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P01375 Protein 1bfc2000-abc0-11e6-9ac8-001a4ae51246 PMC4973837 Two precursor flavonoids (P3G and C3G) and five metabolites (IVA, IVA‐glucuronide, BA‐sulfate, PCA‐3‐sulfate, and VA‐glucuronide) reduced TNF‐α secretion in isolation (Table2).|||Of the combination treatments tested, treatments containing PCA and 4HBA (combination 9); PCA, VA, and 4HBA (combination 10); 4HBA, BA‐glucuronide, and BA‐sulfate (combination 13); and PCA and PCA‐3‐glucuronide (combination 16) significantly reduced TNF‐α secretion (reduction of 4–47%;p≤ 0.050). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P05177 Protein 0a88597e-1b1a-11f0-b759-0050569a791b 10.1016/j.ejps.2024.106735 A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A.|||Discussion A total of 16 glucuronide metabolites of clinically used drugs were screened for their potential to cause time-dependent inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2 and CYP3A. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:A6NDG6 Protein 06e79b20-5c34-11e7-8c5f-001a4ae51246 PMC5286421 Of note, 13-cis-retinoic acid inhibited both Pgp and ABCG2, while its stereoisomer ATRA (all-transretinoic acid) and 9-cis-retinoic acid differing only in the position of thecisdouble bond did not affect the transporters’ activity (seeFigs 1and2andSupplementary Table S1).|||Discussion We have shown that retinol, 13-cis-retinoic acid and retinyl-acetate inhibited both the Pgp- and ABCG2-mediated substrate transport (Fig. 1). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9UNQ0 Protein 06e79b20-5c34-11e7-8c5f-001a4ae51246 PMC5286421 Discussion We have shown that retinol, 13-cis-retinoic acid and retinyl-acetate inhibited both the Pgp- and ABCG2-mediated substrate transport (Fig. 1).|||Of note, 13-cis-retinoic acid inhibited both Pgp and ABCG2, while its stereoisomer ATRA (all-transretinoic acid) and 9-cis-retinoic acid differing only in the position of thecisdouble bond did not affect the transporters’ activity (seeFigs 1and2andSupplementary Table S1). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:63618 Chemical 07b42c36-c47c-11e5-91a7-001a4ae51247 21383204 "Consistent with a previous report, not only gemfibrozil but also its metabolites, gemfibrozil M3 and gemfibrozil glucuronide, could inhibit the uptake of pravastatin by human kidney slices withKivalues similar to those for OAT3 (3.4, 2.7, and 9.9 μM) (Nakagomi-Hagihara et al., 2007) (Table 3).|||The unbound plasma maximum concentrations (Cmax, u) of gemfibrozil and its glucuronide at clinical doses (600 mg twice a day) (Okerholm et al., 1976;Backman et al., 2002;Nakagomi-Hagihara et al., 2007) were enough to cause significant inhibition of pravastatin uptake (Rvalues were 0.60–0.69 and 0.8, respectively), whereas that of gemfibrozil M3 was not high enough (Rvalue was 0.93)." 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006629 Phenotype c69eb3ae-bbe0-11e5-8abe-001a4ae51246 10.1016/j.metabol.2007.02.002 As expected, the 13-cis-retinoic acid therapy induced disturbances in glucose and lipid metabolism.|||Discussion As expected, the 13-cis-retinoic acid therapy induced disturbances in glucose and lipid metabolism. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D008315 Phenotype 4efee8a8-3534-11e8-9192-001a4a160175 21798251 Cell pre-treatment with the glucuronide metabolites significantly inhibited the formation of MDA and fatty acid and cholesterol major oxidation products, HP and 7-keto.|||Pre-treatment with both glucuronide metabolites and HT significantly inhibited MDA production at all tested concentrations although HT was more efficient than the corresponding metabolites. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D014535 Phenotype c07eb51c-c46b-11e5-91a7-001a4ae51247 25380805 "The ability of alternate UDP-sugars, anion transport inhibitors (reported inhibitors of SLC35 transporter proteins), nucleotide reverse-transcriptase inhibitors, and glucuronide conjugates (100µM) to inhibit UDP-GlcUA uptake was assessed at low (2.5µM) and high (1000µM) UDP-GlcUA concentrations (Fig. 3).|||Glucuronide conjugates inhibited the high- and low-affinity components of UDP-GlcUA uptake by 15–40% and 10–20%, respectively." 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype 959dbbb0-ac41-11ee-a19b-0050569a791b PMC7434894 We have shown that activation of multiple kinases and signalling molecules, including RET, PDGFRβ, STAT6 and c-Fos, among others, precedes the morphologic differentiation induced by 13-cis-retinoic acid, and these signalling pathways may contribute to or regulate the subsequent morphologic changes.|||Retinoids are vitamin A analogues that induce tumour cell differentiation,63and 13-cis-retinoic acid treatment of neuroblastoma cells in vitro both induces neuroblastoma cell differentiation and reduces neuroblastoma cell proliferation.64,65–6613-cis-retinoic acid is also currently a component of standard maintenance therapy in the most common protocols utilised for the treatment of children with high-risk neuroblastoma.35Morphologic neuroblastoma cell differentiation induced by retinoids in vitro occurs over the course of 7–10 days, but the pathways activated prior to the morphologic differentiation are poorly understood. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D015951 Phenotype 9c8a9938-bc4a-11e5-ac4e-001a4ae51246 10.1016/j.ejphar.2011.10.009 While conventional parenteral anticoagulants such as unfractionated heparin and low molecular weight heparin also inhibit factor Xa, their mode of action differs to that of darexaban and darexaban glucuronide.|||Results Enzyme assays Both darexaban and darexaban glucuronide inhibited human factor Xa activity in a concentration-dependent manner, withKi values of 0.031±0.003 and 0.020±0.001μM, respectively. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0007165 Phenotype 660f0c10-3c72-11f0-9ac3-0050569a1f61 10.1016/j.fsi.2022.06.025 "Bai The Glucuronide Metabolites of Kaempferol and Quercetin, Targeting to the AKT PH Domain, Activate AKT/GSK3β Signaling Pathway and Improve Glucose Metabolism vol.|||Bai, The glucuronide metabolites of kaempferol and quercetin, targeting to the AKT PH domain, activate AKT/GSK3β signaling pathway and improve glucose metabolism, 82(9) (2021) 104501." 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0042904 Phenotype 5bddfb5c-3554-11e8-a51f-001a4a160176 10606761 This suggests that intracellular 13-cis-retinoic acid levels act specifically to modulate 9-cis-retinoic acid synthesis.|||Possibly more importantly, these data suggest that 13-cis-retinoic acid, a retinoid that is a relatively weak transcriptional regulator, acts to modulate 9-cis-retinoic acid formation through its inhibitory effects oncis-retinol oxidation. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases FPLX:VEGF ProteinFamily c2a79524-cce2-11ee-9aaa-0050569a1f61 10.1016/j.jff.2015.03.019 As compared with high glucose condition, both Uro B and its respective glucuronide, Uro B-gluc, significantly reduced MCP-1 (from 230% to roughly 133% of control), fractalkine (from 153 to 28% and 133% of control for Uro B and Uro B-gluc, respectively) and VEGF expression levels (from 143 to 90% and 48% of control, respectively).|||In cardiomyocytes, the monohydroxylated Uro B and its glucuronide, Uro B-gluc, reduced the levels of MCP-1 and VEGF, while the rest of the urolithins did not exert any effect. 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:CYP ProteinFamily 848fbaf6-ca01-11e5-b88f-001a4ae51247 16299161 "Finally, because it was considered that formation of glucuronide metabolites that can cause clinically significant inhibition of P450 enzymes might be a more widespread phenomenon than was heretofore appreciated, we investigated an experimental design that might be applied generally during preclinical P450 inhibition testing.|||This two-step procedure may serve as a generic method to screen drugs for their ability to be converted to a glucuronide that inhibits P450 enzymes either directly or in a metabolism-dependent manner." 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:SOD ProteinFamily f849f4c2-d3d2-11e5-888a-001a4ae51246 PMC4809317 Precedent of SOD inhibition by xenobiotic metabolites comes from a study byChiou et al. (1999), in which suprofen acyl glucuronide inhibited SOD.|||Prior evidence for SOD inhibition by a glucuronide was reported byChiou and colleagues (1999). 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates FPLX:GSK3 ProteinFamily 660f0c10-3c72-11f0-9ac3-0050569a1f61 10.1016/j.fsi.2022.06.025 "Bai, The glucuronide metabolites of kaempferol and quercetin, targeting to the AKT PH domain, activate AKT/GSK3β signaling pathway and improve glucose metabolism, 82(9) (2021) 104501.|||Bai The Glucuronide Metabolites of Kaempferol and Quercetin, Targeting to the AKT PH Domain, Activate AKT/GSK3β Signaling Pathway and Improve Glucose Metabolism vol." 2 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates FPLX:AKT ProteinFamily 660f0c10-3c72-11f0-9ac3-0050569a1f61 10.1016/j.fsi.2022.06.025 "Bai, The glucuronide metabolites of kaempferol and quercetin, targeting to the AKT PH domain, activate AKT/GSK3β signaling pathway and improve glucose metabolism, 82(9) (2021) 104501.|||Bai The Glucuronide Metabolites of Kaempferol and Quercetin, Targeting to the AKT PH Domain, Activate AKT/GSK3β Signaling Pathway and Improve Glucose Metabolism vol." 2 MESH:D005978 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 2c962c8c-3777-11e8-8f56-001a4a160175 15795089 For example, GSH markedly stimulates the transport of several glucuronide conjugates by MRP1 (Leslie et al., 2001; Sakamoto et al., 1999) and enhances the potency of several inhibitors as well (Chen et al., 2001; Haimeur et al., 2004; Leslie et al., 2001; Loe et al., 1996b, 1998, 2000; Mao et al., 2002). 2 UNIPROT:P03372 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 56e5a69c-cb28-11e5-8189-001a4ae51246 11313362 The expression level and transport activity of the ER transporter(s) identified in our study may modulate glucuronide disposition, and thereby may affect the overall toxicity and activity of glucuronides or glucuronidated compounds. 2 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 0276e662-c8e8-11e5-9cb8-001a4ae51247 17353350 "Because MRP2 is well known to accept various glucuronide conjugates, e.g., estradiol 17β-glucuronide, bilirubin glucuronide, and SN-38 glucuronide (Konig et al., 1999), it can be involved in the luminal efflux of glucuronide conjugates formed in the enterocytes by UGTs." 2 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ebb52ebc-0bf8-11e6-9449-001a4ae51247 10.1074/jbc.275.4.2905 Cumulative evidence indicated that MRP1 and cMOAT/MRP2 mediate the transport of glucuronide and sulfate conjugates of bile salts but not monovalent bile salts (5,6,9,28),e.g.transport studies with membrane vesicles isolated from cDNA-transfected cells revealed that TLC-S is a substrate for human MRP1 (29). 2 UNIPROT:Q92887 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ebb52ebc-0bf8-11e6-9449-001a4ae51247 10.1074/jbc.275.4.2905 Cumulative evidence indicated that MRP1 and cMOAT/MRP2 mediate the transport of glucuronide and sulfate conjugates of bile salts but not monovalent bile salts (5,6,9,28),e.g.transport studies with membrane vesicles isolated from cDNA-transfected cells revealed that TLC-S is a substrate for human MRP1 (29). 2 MESH:D000431 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype fa53b31a-340c-11e8-a34b-001a4a160175 24887323 The question whether accompanying alcohols from ethanolic beverages can cause a significant alcohol glucuronide excretion in urine and thus incorrect DRI®Ethyl Glucuronide Assay results could be the aim of another study. 2 FPLX:G:i activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 0161a1f2-ab8e-11e6-9236-001a4ae51247 PMC4575908 Glucuronide conjugates are reactivated by glucuronide-scavenging β-glucuronidases in the GI microbiota, and such reactivated compounds can significantly damage the GI tract. 2 CHEBI:23053 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical db12386c-67e9-11e8-bbed-001a4a160175 29580974 Because catechins have been shown to be eliminated after Phase II transformation in the body by forming glucuronide, sulfate and methylate conjugates, and for most xenobiotics the conjugated forms are typically less toxic than their parent forms, our review focused on the free form of catechins in the circulation. 2 CHEBI:50985 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 0f8012d0-bbf4-11e5-8abe-001a4ae51246 10.1016/S0003-2697(02)00465-7 This result was expected since glucuronide C6 is reduced by sodium borohydride in methanol during the conversion of the glucuronide methyl ester to the glucoside analog. 2 CHEBI:8988 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical b67c89b6-bc39-11e5-8abe-001a4ae51246 10.1016/j.tips.2006.06.007 SN-38 is mostly eliminated by glucuronidation, the enzymatic conjugation of glucuronic acid to form the more water-soluble metabolite SN-38 glucuronide (SN-38G). 2 CHEBI:8988 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical b64bae12-3406-11e8-bf76-001a4a160175 28347758 SN-38 can be glucuronidated by UDP-glucuronosyltransferases (UGT) in human liver and other tissues, producing the inactive compound SN-38 glucuronide (SN-38G), which is marked for elimination through the bile and into the gastrointestinal tract (Hanioka et al., 2001; Santos et al., 2000; Tukey and Strassburg, 2000; Bock, 2003). 2 UNIPROT:P20585 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 2c962c8c-3777-11e8-8f56-001a4a160175 15795089 For example, GSH markedly stimulates the transport of several glucuronide conjugates by MRP1 (Leslie et al., 2001; Sakamoto et al., 1999) and enhances the potency of several inhibitors as well (Chen et al., 2001; Haimeur et al., 2004; Leslie et al., 2001; Loe et al., 1996b, 1998, 2000; Mao et al., 2002). 2 UNIPROT:P20585 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ebb52ebc-0bf8-11e6-9449-001a4ae51247 10.1074/jbc.275.4.2905 Cumulative evidence indicated that MRP1 and cMOAT/MRP2 mediate the transport of glucuronide and sulfate conjugates of bile salts but not monovalent bile salts (5,6,9,28),e.g.transport studies with membrane vesicles isolated from cDNA-transfected cells revealed that TLC-S is a substrate for human MRP1 (29). 2 CHEBI:9144 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 81eda5d8-3548-11e8-a51f-001a4a160176 18565494 The metabolism of silybin with bovine liver microsomes produced two major glucuronides, 20-OH or 7-OH glucuronide, and a 5-OH glucuronide in a low efficiency[14]. 2 CHEBI:16179 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 5e3f808c-3405-11e8-b868-001a4a160176 28624471 It has been reported that the level of retinyl ester in the lungs of rats was increased by repeating intraperitoneal injections of retinoic acid or retinoyl glucuronide (Barua et al., 2004). 2 UNIPROT:Q8IVM8 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 4fdb0c8a-4e3a-11e6-8f02-001a4ae51247 10.1074/jbc.275.6.4507 The glucuronide moiety might be too large to be accepted by OAT4. 2 CHEBI:65009 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 860f2eba-335f-11e8-bf76-001a4a160175 25623954 In the present study, directN-glucuronidation of AMI to produce quaternary ammonium glucuronide was observed in only human liver microsomes. 2 CHEBI:28870 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 2 CHEBI:64983 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 7329e986-3745-11e8-b868-001a4a160176 26683312 In the same way,Burkhardt et al. (2011)have demonstrated that AOH hydroxylated easily with glucuronide and sulphate acid leading to conjugated metabolites in precision-cut rat liver slices. 2 FPLX:CYP activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 6985e57a-0eb5-11f0-b759-0050569a791b 10.1016/S0955-2863(97)00080-6 [18]Although the parent compounds can be detoxified by ring hydroxylation, once converted to theN-hydroxylamine, the proximal mutagen can be inactivated through conjugation with glucuronide again catalyzed by cytochrome P450 enzymes. 2 MESH:D014529 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype dd86e90e-352a-11e8-a34b-001a4a160175 25065671 AASss are commonly excreted in urine mainly as glucuronide conjugates, the formation of which is catalyzed by various uridine diphosphateglucuronosyltransferase (UGT) enzymes. 2 FPLX:PPAR inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 28ac5962-ca5e-11e5-9bd2-001a4ae51247 12810707 Thus, by stimulating both glucuronidation and transport, PPARα appears to be a key factor for the elimination of many endogenous and exogenous glucuronide derivatives from the liver, at least, in rodents. 2 UNIPROT:Q9NYB5 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 16f22dd8-ca5d-11e5-a3f7-001a4ae51246 12923172 In conclusion, we have characterized Oatp14 in terms of its substrate specificity and localization in the brain and demonstrated that Oatp14 accepts T4, as well as organic anions, including certain glucuronide and sulfate conjugates. 2 CHEBI:89981 decreases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 850deb34-bc4a-11e5-9b9d-001a4ae51247 10.1016/S0014-2999(01)01470-4 It is likely that endotoxin decreases the tubular secretion ofp-nitrophenyl glucuronide, expressed as renal clearance for unbound drug minus glomerular filtration rate. 2 CHEBI:85252 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 6b0820d4-390b-11e8-a51f-001a4a160176 25496917 However, a higher DHEA dose will also increase the levels of 3α-androstanediol glucuronide (ADG) further, which may enhance androgenic effects on the skin. 2 FPLX:GST activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 52010550-c718-11ee-b346-0050569a791b 10.1016/j.lfs.2023.122119 Etoposide and some of its derivates are also inactivated by glutathione and glucuronide conjugations mediated by glutathione S-transferase (GST) and UGT1 enzymes, respectively [72]. 2 UNIPROT:Q9C0C6 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3d36e79a-3419-11e8-a34b-001a4a160175 15212809 The cytotoxicity of CIPC may depend on the initial concentration rather than on that of its major intermediate 4OH-CIPC, because (a) the pretreatment of hepatocytes with the inhibitor of microsomal monooxygenase enhanced CIPC-induced cytotoxicity accompanied by a decrease in the major metabolite 4OH-CIPC and subsequently its glucuronide and/or sulfate, and (b) in isolated hepatic mitochondria, CIPC inhibited both NAD+- and FDA-linked respiration and, with succinate as substrate, the parent compound rather than its metabolites, 4OH-CIPC and 3CA, acted as an uncoupler of oxidative phosphorylation. 2 MESH:D014530 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d6ee82dc-0539-11f0-8fe6-0050569a1f61 10.1016/j.tiv.2024.105888 Irinotecan is a prodrug which undergoes enzymatic decarboxylation by carboxylesterases 1 and 2 to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), before being inactivated via glucuronidation to SN-38 glucuronide (SN-38G) by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) (Alfirevic and Pirmohamed, 2016). 2 MESH:D001728 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 5b6a23b8-377e-11e8-bf76-001a4a160175 10535745 This unexpected discrepancy may have been caused by competitive blockade of APAP conjugation by dicoumarol (reduced APAP sulfate and glucuronide conjugates in bile fluid shown inFigs. 2 CHEBI:24298 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 3f114bbc-aba5-11e6-9ac8-001a4ae51246 PMC4545316 Following ingestion, the majority of BPA is quickly bound to glucuronic acid to produce BPA glucuronide (BPA-G), a metabolic process called glucuronidation that is carried out by enzymes primarily in the liver and gut (NTP, 2008). 2 CHEBI:24298 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical b67c89b6-bc39-11e5-8abe-001a4ae51246 10.1016/j.tips.2006.06.007 SN-38 is mostly eliminated by glucuronidation, the enzymatic conjugation of glucuronic acid to form the more water-soluble metabolite SN-38 glucuronide (SN-38G). 2 MESH:D004610 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype f93ceaca-48f2-11f0-8cae-0050569a1f61 10.1016/j.jff.2016.08.024 It has been reported in recent years that ETs are hydrolysed in mammals to ellagic acid under physiological conditions, and that ellagic acid is then gradually metabolised by the intestinal microbiota to produce different types of urolithins (hydroxy-6H-dibenzopyran-6-one derivatives) and dimethyl-ellagic acid glucuronide (Bialonska et al., 2010; Landete et al., 2015; Seeram et al., 2006). 2 MESH:D002110 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype b8492072-374f-11e8-bf76-001a4a160175 28416362 We therefore decided to test this hypothesis by investigating thein vitroultrasound-induced activation of a glucuronide anticancer prodrug on cancer cells. 2 MESH:D000432 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 0f8012d0-bbf4-11e5-8abe-001a4ae51246 10.1016/S0003-2697(02)00465-7 This result was expected since glucuronide C6 is reduced by sodium borohydride in methanol during the conversion of the glucuronide methyl ester to the glucoside analog. 2 UNIPROT:P22309 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein d6ee82dc-0539-11f0-8fe6-0050569a1f61 10.1016/j.tiv.2024.105888 Irinotecan is a prodrug which undergoes enzymatic decarboxylation by carboxylesterases 1 and 2 to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), before being inactivated via glucuronidation to SN-38 glucuronide (SN-38G) by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) (Alfirevic and Pirmohamed, 2016). 2 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein e02ff613-f590-11eb-8e3c-001a4a160175 31691077 SN-38 is mainly cleared via glucuronidation catalyzed by UDP-glucuronosyltransferase 1A1 (UGT1A1) to SN-38 glucuronide (SN-38G) [2,3]. 2 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein af84219a-c8e7-11e5-a1fd-001a4ae51246 17577039 "SN-38 biliary excretion is enhanced by the formation of SN-38 glucuronide (SN-38G), which is catalyzed primarily by the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1).13 UGT1A1 catalyzes transfer of a glucuronic acid moiety from the cofactor uridine diphosphoglucuronic acid (UDPGA) to bilirubin and insoluble xenobiotics (eg, SN-38)." 2 UNIPROT:O15438 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 889c774e-bc0d-11e5-9b9d-001a4ae51247 PMC3524273 ABCC3 (MRP3) mediates the transport of glucuronide conjugates, taurocholate, glycocholate and methotrexate. 2 UNIPROT:P46721 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 1f80f950-0501-11f0-baad-0050569a1f61 10.1016/j.taap.2024.117040 OATP activity in a downstream hepatocyte would then allow efficient reuptake of this glucuronide, again with a possibility of being excreted into the bile. 2 UNIPROT:P10632 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein f29979e4-0532-11f0-8fe6-0050569a1f61 10.1016/j.dmpk.2024.101023 Based on human elimination study, it is known that rosiglitazone gets excreted almost completely via metabolism [7,15] Further,in vitrometabolism studies suggested involvement of P450's in metabolism with major contribution of CYP2C8 (>50 % inhibition with 13-cis-retinoic acid) and minor by CYP2C9 enzymes. 2 CHEBI:17859 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 3d12c1bb-e1e6-11e9-a35a-001a4a160175 PMC6760779 Among the three, only glutaric acid significantly increased the uptake of [ H]-estrone sulfate, [ H]-estradiol glucuronide, [ H]-androstanediol glucuronide, and [ H]-taurocholic acid (Fig 3F). 2 UNIPROT:P42771 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 6bde13ec-3938-11e8-bf76-001a4a160175 12628307 Screening the formation of each glucuronide using RLM, DLM, MLM, and HLM allowed for the selection of microsomes from a species efficient in the production of each particular glucuronide(Table 1). 2 UNIPROT:P00176 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein b43a9a9e-bbee-11e5-8abe-001a4ae51246 10.1016/S0006-8993(02)03546-1 Considering that doxorubicin is metabolized by aldo-keto reductase, cytochrome P450 (including CYP2B1) and glucuronide conjugating enzymes[2,3,13,37,39], we may put forward the possibility that SLT-II-induced increases in the brain concentrations of doxorubicin are, in part, due to reductions in the metabolism which occurs in the brain. 2 UNIPROT:O00186 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ab92e68e-bc03-11e5-8abe-001a4ae51246 10.1016/j.fct.2006.03.007 Previous in vivo study in the rat showed that the phase II metabolites of paracetamol (glucuronide and sulphate) were significantly increased by PSP, which may reflect either phase II enzyme induction or a decrease rate of metabolism which utilized the phase I pathways (Yeung et al., 1995). 2 UNIPROT:O00186 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ac2bb95e-bc03-11e5-9b9d-001a4ae51247 10.1016/j.fct.2006.03.008 Further studies showed that the phase II metabolites of paracetamol (glucuronide and sulphate) were significantly increased by PSP, which may reflect a decrease rate of metabolism through the phase I pathway (Yeung et al., 1995). 2 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily b64bae12-3406-11e8-bf76-001a4a160175 28347758 SN-38 can be glucuronidated by UDP-glucuronosyltransferases (UGT) in human liver and other tissues, producing the inactive compound SN-38 glucuronide (SN-38G), which is marked for elimination through the bile and into the gastrointestinal tract (Hanioka et al., 2001; Santos et al., 2000; Tukey and Strassburg, 2000; Bock, 2003). 2 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily dd86e90e-352a-11e8-a34b-001a4a160175 25065671 AASss are commonly excreted in urine mainly as glucuronide conjugates, the formation of which is catalyzed by various uridine diphosphateglucuronosyltransferase (UGT) enzymes. 2 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 21a775a0-dcad-11ea-a59d-001a4a160175 29427741 MPA glucuronide (MPAG) and MPA acyl glucuronide (AcMPAG) are primarily produced by UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7, respectively[6], and thein vitropharmacological activity of AcMPAG indicates roles in the gastrointestinal toxicity of MPA[7]. 2 CHEBI:37924 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 326ccd20-c472-11e5-85e4-001a4ae51246 19546238 "Atazanavir inhibits the UDP-glucuronosyltransferase isoenzyme 1A1 (UGT1A1), the enzyme responsible for bilirubin glucuronidation, causing decreased glucuronide excretion that may result in jaundice." 2 MESH:D016572 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 4cc7bd9e-3552-11e8-9fbf-001a4a160176 19857666 But because the pharmacokinetics of MMF exhibit a high degree of inter- and intraindividual variability and because cyclosporine (CsA) may inhibit the biliary excretion of mycophenolic acid glucuronide (MPAG), it is possible that outcomes could be improved with MPA and MPAG monitoring, especially in association with experimental immunosuppressive protocols.1 There is evidence that monitoring of MPA and MPAG may diminish adverse drug toxicity and improve long-term kidney transplant function. 2 CHEBI:16189 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 8e2e3432-0540-11f0-8fe6-0050569a1f61 10.1016/j.steroids.2024.109441 Unintended sulfate hydrolysis increases indirectly determined glucuronide concentrations and is unrecoverable even with a suitable internal standard. 2 CHEBI:8764 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 5aa695a2-c475-11e5-8491-001a4ae51247 25600919 The pharmacokinetics of MMF in patients with end-stage renal disease indicated that renal failure prolongs the half-life of glucuronide, causing the accumulation of the mycophenolic acid glucuronide (MPAG) and increasing the free non-protein-bound fraction of mycophenolic acid (MPA) (f-MPA)[18–21]. 2 CHEBI:8764 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 59f1d900-c8e9-11e5-a1fd-001a4ae51246 18463325 "Pharmacokinetics of MMF in kidney transplant with renal insufficiencies and ESRD patients indicated that renal failure prolongs the half-life of glucuronide, causes accumulation of the glucuronide metabolite (MPAG) and increases the free non-protein-bound fraction of MPA (f-MPA) [26,27]." 2 CHEBI:39867 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 588430fe-f121-11ee-9133-0050569a1f61 10.1016/S0006-2952(03)00076-5 Co-administration of valproic acid significantly decreased the normally extensive first pass metabolism of AZT to its glucuronide conjugate and increased the ratio of urinary AZT glucuronide to unconjugated AZT by 50%. 2 CHEBI:39867 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 588430fe-f121-11ee-9133-0050569a1f61 10.1016/S0006-2952(03)00076-5 Valproic acid has also been shown to inhibit the formation of 4-hydroxyandrostendione glucuronide, a synthetic steroid, in bothin vitroandin vivorat studies[18]an indication that valproic acid may also be able to interfere with the glucuronidation of steroids. 2 MESH:D000077731 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 3f0c7da0-3360-11e8-bf76-001a4a160175 25578527 Studies in rabbit models show how meropenem accelerates glucuronidation of VPA to VPA glucuronide (VPA-G) and inhibits deconjugation, which increases VPA and VPA-G clearance.11,30Another study in mice with panipenem showed that this antibiotic inhibited enzyme induction and allosteric activation of glucuronisil UPD-transferase, which is responsible for VPA glucuronidation. 2 UNIPROT:O60656 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3c3b3408-bbea-11e5-8abe-001a4ae51246 10.1016/j.molmed.2005.04.008 Thus, contrary to the protective effect of hyperbilirubinemia, the risk of cancer might be increased by UGT1 polymorphisms that impair glucuronide conjugation and thus the detoxification of carcinogens[73–75]. 2 CHEBI:29309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 02016d0a-bc1e-11e5-9b9d-001a4ae51247 10.1016/j.jchromb.2013.09.023 In the same way, the metabolitesM7aandM7b(m/z343.1024, C15H19O9, eluted at 8.34 and 8.66min, respectively) were 14Da higher thanM5aorM5b, indicating that they were a pair of successive methyl products of HT glucuronide conjugations (HMVAlc glucuronide conjugations). 2 CHEBI:72544 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 6c4b278c-bc19-11e5-9b9d-001a4ae51247 PMC2277483 The enzymatic incubations of the other five flavonoids (luteolin, eriodictyol, quercetin, hesperetin, and myricetin) all produced more than one glucuronide derivative. 2 UNIPROT:Q9UNQ0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 8089e29a-c463-11e5-85e4-001a4ae51246 PMC4905824 "Pharmacokinetic studies involving 4-methylumbelliferone and ethinyl estradiol demonstrate that Bcrp (Abcg2) mediates the transport of glucuronide and sulfate [21,22]." 2 CHEBI:28747 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical de59daf6-3757-11e8-b868-001a4a160176 PMC5146996 Herein, we report the development and validation of a new stable isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry (SID-LC-ESI–MS/MS) method using picolinic acid derivatization that allows us to simultaneously quantify nine human hydroxy-androgens and their glucuronide and sulfate conjugates, including a panel of hydroxy-androgens involved in androgen metabolism in prostate (rectangle circled inScheme 1). 2 CHEBI:30768 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a4ce85da-bc47-11e5-8abe-001a4ae51246 10.1016/j.aca.2005.07.046 In vivo it gets bio-transformed into various metabolites, namelyp-fluorobenzol propionic acid, 4-(4-chlorophenyl-4 hydroxy piperedine, pyridinium metabolite, reduced haloperidol and haloperidol glucuronide. 2 UNIPROT:Q92887 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein f6dcf5b4-c471-11e5-85e4-001a4ae51246 20028753 "The finding thatAbcb1a/1b;Abcc2−/−mice had similarly elevated Ugt1a1 expression, but strongly reduced biliary excretion of etoposide glucuronide (≤0.5% of the dose) compared withAbcb1a/1b−/−mice (10% of the dose;Fig. 3A), indicates that Abcc2 must be responsible for the biliary output of the glucuronide metabolite.|||Indeed, Abcc2-deficient mice had up to 7-fold increased urinary output of etoposide glucuronide compared with their WT counterparts (Fig. 2C)." 2 UNIPROT:P08236 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 4165f5e4-3c96-11f0-afc2-0050569a791b 10.1016/j.scitotenv.2022.154693 " 703 2020 135536 Zhang J, Liu ZH, Zhong S S, Wang H, Caidan B, Yin H, Dang Z. Strategy for effective inhibition of arylsulfatase/beta-glucuronidase to prevent deconjugation of sulfate and glucuronide conjugates in wastewater during sample collection and storage.||| Liu S.S. Zhong H. Wang B. Caidan H. Yin Z. Dang Strategy for effective inhibition of arylsulfatase/beta-glucuronidase to prevent deconjugation of sulfate and glucuronide conjugates in wastewater during sample collection and storage Sci." 2 CHEBI:18268 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 6b261dde-5caa-11e7-9833-001a4ae51246 26658676 Moreover, glucurolactone reduced daidzin absorption and daidzein glucuronide excretion in the perfusate sample containing glucose (Fig. 3, G–I), which is consistent with previous reports (Liu and Hu, 2002).|||By contrast, glucurolactone concentration dependently reduced the absorption of daidzin, which was selected as the positive control, and the excretion of daidzin glucuronide in the perfusate sample (Fig. 3, G–I). 2 CHEBI:49468 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 78c60c08-bc45-11e5-9b9d-001a4ae51247 10.1016/S0378-4347(01)00366-8 The glucuronide ofO-demethyl tramadol was synthesized by Bayer AG (Wuppertal, Germany).|||ForO-demethyl tramadol glucuronide the amount of the reference compound synthesised by Bayer AG Wuppertal Germany was insufficient for a full validation. 2 CHEBI:28821 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical da680bf0-c47e-11e5-85e4-001a4ae51246 20089784 "The use of 200μmol/L of piperine reduced the amount oftrans-resveratrol glucuronide secreted back to the intestinal lumen from 82.6 ± 6.2 (n= 57) to 37.8 ± 4.2 (n= 6) pmol/(5 min·|||Incubations with 200μmol/L of piperine decreased the secretion oftrans-resveratrol glucuronide by 54% without any modification in the uptake of the parent compound or in the secretion of the sulfate conjugate." 2 UNIPROT:Q16769 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a929a800-2c61-11f0-b759-0050569a791b 10.1016/S0024-3205(02)01917-3 Introduction Antibody directed enzyme prodrug therapy (ADEPT) using glucuronide prodrugs activated by the human lysosomal enzyme β-glucuronidase (EC 3.2.1.31) is an experimental approach to enhance tumor selectivity and reduce systemic toxicity of anti-cancer agents.|||Antibody directed enzyme prodrug therapy (ADEPT) using glucuronide prodrugs activated by the human lysosomal enzyme β-glucuronidase (EC 3.2.1.31) is an experimental approach to enhance tumor selectivity and reduce systemic toxicity of anti-cancer agents. 2 CHEBI:6619 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 0aae6d66-5ca1-11e7-b441-001a4ae51247 26758854 However, the significant increase in glucuronide accumulation caused by MK-571 was strong evidence that one or more MRP family proteins contributed to cellular excretion of resveratrol glucuronides (Fig. 1B).|||By contrast, MK-571 led to a significant elevation (>140%,P< 0.05) in glucuronide accumulation (Fig. 1B). 2 MESH:D005445 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 834dc114-c9fd-11e5-be63-001a4ae51246 14977865 "Diclofenac and flunitrazepam inhibited formation of the phenolic glucuronide by human liver and jejunum microsomes.|||Diclofenac and flunitrazepam inhibited the formation of benzylic glucuronide by human jejunum microsomes as well as from UGT2B7 Supersomes." 2 MESH:D051379 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype f6dcf5b4-c471-11e5-85e4-001a4ae51246 20028753 "Indeed, Abcc2-deficient mice had up to 7-fold increased urinary output of etoposide glucuronide compared with their WT counterparts (Fig. 2C).|||The finding thatAbcb1a/1b;Abcc2−/−mice had similarly elevated Ugt1a1 expression, but strongly reduced biliary excretion of etoposide glucuronide (≤0.5% of the dose) compared withAbcb1a/1b−/−mice (10% of the dose;Fig. 3A), indicates that Abcc2 must be responsible for the biliary output of the glucuronide metabolite." 2 MESH:D051379 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype b4546244-3c6d-11f0-9ac3-0050569a1f61 10.1016/j.ejpb.2022.06.008 "However, these changes were not rescued in mice overexpressing human OATP1B1 or human OATP1B3 in liver, although this did partially reverse the altered cintirorgon glucuronide pharmacokinetics in Oatp1a/1b−/− mice.|||However, these changes were not rescued in mice overexpressing human OATP1B1 or human OATP1B3 in liver, although this did partially reverse the altered cintirorgon glucuronide pharmacokinetics in Oatp1a/1b−/− mice." 2 MESH:D004008 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 834dc114-c9fd-11e5-be63-001a4ae51246 14977865 "Diclofenac and flunitrazepam inhibited the formation of benzylic glucuronide by human jejunum microsomes as well as from UGT2B7 Supersomes.|||Diclofenac and flunitrazepam inhibited formation of the phenolic glucuronide by human liver and jejunum microsomes." 2 MESH:D003474 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d9937bc8-c688-11ee-9aaa-0050569a1f61 10.1016/j.biopha.2023.116034 Tetrahydrocurcumin, hexahydrocurcumin, octahydrocurcumin, and hexahydrocurcuminol are produced via metabolic O-conjugation of curcumin, which also produces curcumin glucuronide and curcumin sulfate.|||Additionally, reduced curcumin is used for glucuronidation to produce curcumin glucuronide, curcumin sulfate, dihydro-curcumin-glucuronide, and tetrahydrocurcumin-glucuronide[25]. 2 MESH:D019888 decreases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 4417c378-c6e8-11ee-8b99-0050569a1f61 10.1016/j.tiv.2023.105689 Nelfinavir did not decrease glucuronide levels up to a concentration of 10 μM. Discussion We recently evaluated a 3D culture system using cell-able plates for bilirubin glucuronidation activity in canine and human hepatocytes (Omori et al., 2022), wherein it has been confirmed that the morphology of human hepatocyte spheroids is maintained until day 14, as previously reported (Ogihara et al., 2017), and canine hepatocyte spheroids form distinct spheroidal shapes until day 14.|||Nelfinavir treatment did not decrease glucuronide levels up to 10 μM. 2 PF:PF03021 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily ce0869b4-bc44-11e5-8d2d-001a4ae51247 PMC3493972 In addition, although cell-CAM 105 was identified to be an ATP-dependent taurocholate transporter, CM2 could partially inhibit ATP-dependent glucuronide uptake of CMVs (Figure 4B).|||Kouzukiet al.found that indomethacin glucuronide transport clearance across the bile canalicular membrane in hepa Eisai hyperbilirubinemic rats (EHBR) with MRP2 function hereditarily defective was approximately 50% that in Sprague-Dawley rats (SDRs).24Nishinoet al.confirmed that no significant difference was observed in the biliary excretion of BIBR 277 glucuronide between SDRs and EHBR, although the plasma disappearance of BIBR 277 glucuronide was delayed in EHBR.25In our study, we found that CM2 antigen could inhibit ATP-dependent glucuronide uptake of CMVs (Figure 4B) and contribute to the glucuronide excretion. 2 UNIPROT:P28607 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 4165f5e4-3c96-11f0-afc2-0050569a791b 10.1016/j.scitotenv.2022.154693 " 703 2020 135536 Zhang J, Liu ZH, Zhong S S, Wang H, Caidan B, Yin H, Dang Z. Strategy for effective inhibition of arylsulfatase/beta-glucuronidase to prevent deconjugation of sulfate and glucuronide conjugates in wastewater during sample collection and storage.||| Liu S.S. Zhong H. Wang B. Caidan H. Yin Z. Dang Strategy for effective inhibition of arylsulfatase/beta-glucuronidase to prevent deconjugation of sulfate and glucuronide conjugates in wastewater during sample collection and storage Sci." 2 CHEBI:16234 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical c240c60c-bbf0-11e5-9b9d-001a4ae51247 10.1016/S0960-894X(03)00466-9 Synthesis We attempted to synthesize the glucuronide and glucoside of WAY-123783 by the Mitsunobu procedure.11Phenolic OH and a nitrogen atom in the pyrazole ring of WAY-123783 were thought to be the reaction site.|||We attempted to synthesize the glucuronide and glucoside of WAY-123783 by the Mitsunobu procedure.11Phenolic OH and a nitrogen atom in the pyrazole ring of WAY-123783 were thought to be the reaction site. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P16109 Protein 70f51fdc-bc4a-11e5-8abe-001a4ae51246 10.1016/j.ejphar.2012.11.026 Darexaban glucuronide did not induce platelet activation, while 100μM darexaban significantly reduced the expression of CD62P and activated GPIIb/IIIa at the basal level. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:A8MT33 Protein 2c4db188-bc08-11e5-9b9d-001a4ae51247 10.1016/j.peptides.2011.09.020 The pharmacokinetics of morphine and its M3G glucuronide conjugate showed respective decreases and increases in a rat model of streptozotocin-induced diabetes and the expression of MRP2, MRP3 and UGT2Bi in the liver[249]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:A8MT33 Protein 9a870ddc-c8e9-11e5-9ad8-001a4ae51247 PMC2657472 "In this animal model, biliary excretion of glucuronide and glutathione conjugates was reduced to negligible levels, implicating a major role for Mrp2 in their disposition." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:A8MT33 Protein 5a6c35b2-c482-11e5-9cc6-001a4ae51246 23132334 MRP2 inhibition by DTG and its ether glucuronide, M2, was assessed by measuring the uptake of [3H]EG in MRP2 membrane vesicles. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:A8MT33 Protein 271e3536-cb8d-11e5-8106-001a4ae51247 10997931 "In addition, the ATP-dependent uptake of DNP-SG, a typical substrate for cMOAT/MRP2, by canalicular membrane vesicles was inhibited by BIBR 277 and its glucuronide in a concentration-dependent manner withKivalues of 3.44 ± 0.37 and 1.81 ± 0.30 μM, respectively, suggesting that both BIBR 277 and BIBR 277 glucuronide have an affinity for cMOAT/MRP2." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:A8MT33 Protein da680bf0-c47e-11e5-85e4-001a4ae51246 20089784 However, secretion of glucuronide and sulfate conjugates decreased, thus implicating MRP2 in its efflux. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q92887 Protein 271e3536-cb8d-11e5-8106-001a4ae51247 10997931 "In addition, the ATP-dependent uptake of DNP-SG, a typical substrate for cMOAT/MRP2, by canalicular membrane vesicles was inhibited by BIBR 277 and its glucuronide in a concentration-dependent manner withKivalues of 3.44 ± 0.37 and 1.81 ± 0.30 μM, respectively, suggesting that both BIBR 277 and BIBR 277 glucuronide have an affinity for cMOAT/MRP2." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 phosphorylatesProtein UNIPROT:Q99683 Protein 5aec7b36-c8e8-11e5-9ad8-001a4ae51247 17961201 Hydrogen peroxide-induced de-phosphorylation of ASK1 (Ser967) was not significantly attenuated by pre-treatment of cortical neurons with hesperetin, its glucuronide or 5-nitro-hesperetin (0.1 μmol/L; 18 h) prior to the addition of H2O2(Fig. 3a). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:O15439 Protein fa4f7cda-c8e5-11e5-9624-001a4ae51246 17682070 "If the kidney concentrations of edaravone glucuronide at the clinical dose (30 mg/man) can inhibit MRP4, it can be speculated that edaravone may increase kidney concentrations of some cephalosporins." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:O15439 Protein 10a31396-ca00-11e5-9b70-001a4ae51247 15504935 MK571 and the glucuronide conjugates of α-naphthol,p-nitrophenol, and phenolphthalein, which have been shown to interact with MRP2 (28), also inhibited MRP4 (Table 2andFigure 4). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9NPD5 Protein 24b5f95a-84f3-11ee-add2-0050569a791b PMC9474414 Bempedoic acid and its glucuronide weakly inhibit OATP1B1 and OATP1B3 at clinically relevant concentrations, raising simvastatin blood levels3. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q13505 Protein a9c687b6-c8e7-11e5-9cb8-001a4ae51247 17578901 "Because NSAIDs are mainly excreted into the urine as the glucuronide-conjugated form (Davies and Anderson,1997a,b), we evaluated the inhibitory effect of diclofenac and naproxen glucuronide, which were prepared biosynthetically in vitro, on MRP2-mediated transport of MTX (Fig. 5E)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P00734 Protein 9c8a9938-bc4a-11e5-ac4e-001a4ae51246 10.1016/j.ejphar.2011.10.009 Darexaban and darexaban glucuronide suppressed prothrombin activation by free factor Xa, prothrombinase, and whole blood clot with similar potencies, with IC50values ranging from 25 to 82nM. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P29466 Protein bfb26c00-5c31-11e7-8c5f-001a4ae51246 PMC5263152 In particular, treatment with wogonoside, a glucuronide metabolite of the bioactive flavonoid wogonin, reduced significantly colonic NF-κB and NLRP3 expression, as well as caspase-1 expression and activity in mice with colitis, exerting beneficial effects on colonic inflammation (69). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P11926 Protein 5e484890-d31b-11e5-aade-001a4ae51247 PMC319675 13-cis-Retinoic acid inhibited this ornithine decarboxylase induction when painted on the skin 1 hr before these natural products. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P11926 Protein 802d4bac-d381-11e5-b6ad-001a4ae51246 7371022 ANFT-induced ornithine decarboxylase activity was principally localized in the bladder epithelium and was inhibited in a linear dose-response relationship by the synthetic retinoid, 13-cis-retinoic acid. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P03973 Protein 0566eaaa-bbd9-11e5-8abe-001a4ae51246 10.1016/j.nutres.2012.09.018 Another study by the same group demonstrated that hesperetin-7-O-glucuronide, a form of conjugated glucuronide hesperidin, stimulated osteoblast differentiation by up-regulating mRNA gene expression (eg, ALP, Runx2, and osterix) and induced phosphorylation of Smad1/5/8 in primary rat osteoblasts[59]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:O00206 Protein 15cdb300-bc34-11e5-8abe-001a4ae51246 PMC4164621 TLR4 activation is not limited to pathogen detection; recent publications suggest that opioids and their glucuronide metabolites, among other ligands, can elicit TLR4-dependent activation in glial and neuronal cells[9],[10],[11],[12],[13],[14]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:Q96EB6 Protein 0d007230-bc20-11e5-8abe-001a4ae51246 PMC4245563 On the other hand, our results showed that resveratrol, but not its glucuronide and sulfate conjugates, upregulated SIRT1 expression. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q06327 Protein 6bec5c7e-bc2e-11e5-8abe-001a4ae51246 10.1016/j.bmc.2010.10.012 Inhibitors of LOX have attracted attention initially as potential agents for the treatment of inflammatory and allergic diseases, certain types of cancer and cardiovascular diseases.33,34Goldreich et al.35examined the effect of retinol,all-trans-retinoic acid and 13-cis-retinoic acid on the activity of lipoxygenase-1 and lipoxygenase-2 towards linoleic acid.All-trans-retinoic acid and 13-cis-retinoic acid inhibited lipoxygenase-1 activity competitively, whereas retinol inhibited lipoxygenase-1 activity in a mixed manner. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q06327 Protein 3678a452-bc1b-11e5-8abe-001a4ae51246 10.1016/j.ejmech.2009.10.012 Goldreich et al[25]examined the effect of retinol,all-trans-retinoic acid and 13-cis-retinoic acid on the activity of lipoxygenase-1 and lipoxygenase-2 towards linoleic acid.All-trans-retinoic acid and 13-cis-retinoic acid inhibited lipoxygenase-1 activity competitively, whereasall-trans-retinol inhibited lipoxygenase-1 activity in a mixed manner. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P10145 Protein 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 Ibuprofen-acyl glucuronide reduces interleukin-8 release evoked by TRPA1 stimulation from bronchial epithelial cells TRPA1 expressed by various non-neuronal cells of the airways elicits calcium responses and the release of proinflammatory cytokines, including interleukin-8 (IL-8) [25–27]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P00738 Protein 4efee8a8-3534-11e8-9192-001a4a160175 21798251 Cell pre-treatment with the glucuronide metabolites significantly inhibited the formation of MDA and fatty acid and cholesterol major oxidation products, HP and 7-keto. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P00746 Protein f08aeb6a-c8dd-11e5-9ad8-001a4ae51247 16928785 "The discrepancy between the combined DF glucuronide + 4′-OH DF formation and total consumption during the subsequent period (Fig. 3B) was suggestive of significant formation of secondary or sequential metabolites, probably to glucuronide and glutathione products of the hydroxyl DF (Tang et al., 1999;Kumar et al., 2002)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P08246 Protein 1980ad42-ae93-11ec-840e-0050569a791b PMCPMC8394930 Several flavonoid glucuronide derivatives at 1 μM inhibited NE release by 30–50% and at 10 μM, decreased ROS release by 50–70% from activated neutrophils [142]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:A1Z6E0 Protein ae5803a6-c67f-11ee-9133-0050569a1f61 10.1016/j.aca.2023.342007 Therefore, the analogue of glucuronide, MetGlu, was added to induce the expression of GUS to accelerate the enzymatic reaction (Fig. 3C). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:O43557 Protein a11da750-bbf6-11e5-9b9d-001a4ae51247 PMC4466618 Valproic acid is a glucuronide inhibitor which increases the half-life of LTG and decreases its clearance.39Owing to this inhibitory effect, LTG starting and maintenance doses are recommended to be lower during concurrent valproic acid therapy. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y5S8 Protein 677020fc-ab5e-11e6-9646-001a4ae51246 PMC5021119 Quercetin and quercetin‐3‐O‐glucuronide (1 μM) inhibited NOX activity in vascular smooth muscle cells ex vivo from both spontaneously hypertensive rats and normotensive Wistar Kyoto rats, and this effect was abolished by the β‐glucuronidase inhibitor, saccharolactone, indicating that the active aglycone is generated in situ134. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P35228 Protein e600338e-f58a-11eb-8bfd-001a4a160175 30735752 Conclusions This study highlighted for the first time the ability of HT and Tyr sulfate and glucuronide metabolites to inhibit iNOS-derived NO overproduction in intestinal Caco-2  1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P01308 Protein 1d3ec51c-bc4c-11e5-ac4e-001a4ae51246 10.1016/j.exppara.2007.06.008 A number of nitro-thiazolides, including NTZ, TIZ and also tizoxanide glucuronide (TIG; seeTable 1) inhibited insulin crosslinking activity to less than 35% of the control value (Fig. 3b). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P0DSE1 Protein 3776b206-5c31-11e7-af4d-001a4ae51247 PMC5344956 Hydroxyponatinib glucuronide (M24) contributed 5.1% to the TRA in urine. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P09601 Protein b15117b6-eb7b-11ee-8b99-0050569a1f61 10.1016/j.jdsr.2013.07.003 Since chondrogenesis is a prerequisite for bone formation, isotoretinoin (13-cis-retinoic acid) had been tested to prevent HO in fibrodysplasia ossificance progressiva patients (Fig. 2). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:P41159 Protein 78051312-bc32-11e5-8d2d-001a4ae51247 PMC3661556 Effects of Resveratrol and its Metabolites on Leptin Expression As far as maturing pre-adipocytes are concerned, resveratrol reduced, whiletrans-resveratrol-3-O-sulfate increased, leptin mRNA levels No changes were induced by glucuronide metabolites (Figure 3A). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P41159 Protein 78051312-bc32-11e5-8d2d-001a4ae51247 PMC3661556 However, glucuronide metabolites reduced leptin secretion to the media, and resveratrol andtrans-resveratrol-3-O-sulfate showed a tendency towards reduced values (Figure 3B). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:O75469 Protein fd3bae24-bc37-11e5-ac4e-001a4ae51246 PMC3398007 Thus, we tested whether baicalein and its glucuronide metabolite, baicalin would induce PXR expression in LS174T colon cancer cellsin vitro. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:O75469 Protein fd3bae24-bc37-11e5-ac4e-001a4ae51246 PMC3398007 We also showed that baicalin, a glucuronide-modified analogue of baicalein, is unable to induce Cdx2 and/or PXR and that it does not activate PXRin vitroorin vivo. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P21549 Protein 3e5ce8b2-c473-11e5-91a7-001a4ae51247 PMC2964280 "Materials and Methods Study population and epidemiologic data The subjects included in this study were participants enrolled (1991-1999) in the Retinoid Head and Neck Second Primary Trial designed to evaluate whether daily low-dose 13-cis-retinoic acid (13-cRA) prevents SPT or tumor recurrence in early-stage HNSCC patients (1)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q07507 Protein b7915338-ef45-11e5-9b35-001a4ae51246 22329675 Darexaban and darexaban glucuronide (10 μmol L−1) tended to produce a DPT ratio (DPTR) that was similar to or even lower than PTR, regardless of the thromboplastin reagent used. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P21964 Protein be4de0d0-bc3a-11e5-8d2d-001a4ae51247 10.1016/j.mam.2010.09.005 Phase II products are also produced and methyl ethers (products of COMT) as well as different glucuronide conjugates are detected in different tissues and in urine. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P18502 Protein d0b66a5a-865e-11e6-a316-001a4ae51247 27669199 Therefore,M54was tentatively identified as a glucuronide conjugation product of PTC. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q9HAW8 Protein 2792e8e6-c466-11e5-a92e-001a4ae51246 23288867 2, B and C), the main glucuronide products of UGT1A10 in both cases (Fig. 2), are the 3-glucuronide of each of these estriol stereoisomers. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q8TXY4 Protein 8852afde-c8e6-11e5-9ad8-001a4ae51247 17431030 "Therefore, most of the parent compound present in feces is likely the result of enzymatic hydrolysis of M2, which suggests that MK-0524 was eliminated primarily by metabolism via glucuronidation and further excretion of the acyl glucuronide into bile and feces." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:P05231 Protein 66553656-bbdd-11e5-9b9d-001a4ae51247 PMC4480174 The acyl glucuronide metabolite of MPA (AcMPAG) may also have a role in inflammation and has been found in mononuclear cell cultures to stimulate the release of interleukin-6 and tumor necrosis factor-a via an increase in production of mRNA [3]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P22309 Protein d3d14fda-c484-11e5-85e4-001a4ae51246 22674635 UGT1A1 Polymorphisms SN38 is inactivated by the addition of a glucuronide moiety byUGT1A1, the activity of which is reduced in individuals who have genetic polymorphisms likeUGT1A1*28.16,17Patients who are heterozygous or homozygous forUGT1A1*28may have a lower than normal capacity to metabolize irinotecan and are at greater risk for adverse effects associated with the use of standard doses of irinotecan14and, presumably, SN38. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P22309 Protein a20f440c-3b51-11e8-8636-001a4a160175 PMC6017115 Similarly, it has been reported that gemfibrozil inhibits repaglinide glucuronidation via UGT1A1, because gemfibrozil and gemfibrozil glucuronide (a main metabolite of gemfibrozil) inhibit UGT1A1 together [30]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:O15438 Protein 2c4db188-bc08-11e5-9b9d-001a4ae51247 10.1016/j.peptides.2011.09.020 The pharmacokinetics of morphine and its M3G glucuronide conjugate showed respective decreases and increases in a rat model of streptozotocin-induced diabetes and the expression of MRP2, MRP3 and UGT2Bi in the liver[249]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein fb1964ac-c8e8-11e5-9624-001a4ae51246 18268076 "For example, based on in vitro inhibition studies, it has been suggested that CYP2C8 inhibition by gemfibrozil acyl glucuronide substantially contributed to the severe toxicity of the lipid-lowering drug cerivastatin when coadministered with gemfibrozil (Shitara et al., 2004;Ogilvie et al., 2006)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein ee3873b0-ca03-11e5-b88f-001a4ae51247 15998357 gemfibrozil glucuronide is a potent inhibitor of CYP2C8 (Shitaraet al.2004). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein 14d874da-8df7-11e7-a20e-001a4ae51247 27298339 Similar to what was noted for acyl glucuronide inhibitors of CYP2C8, other non-P450s that play a role in catalyzing functionalization reactions (phase I reactions) have also produced metabolites that inhibit P450. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein 36f49570-3910-11e8-b868-001a4a160176 PMC6175296 DISCUSSION Montelukast has been suggested as a CYP2C8 probe substrate due to the central role of CYP2C8 in its oxidative metabolism and its sensitivity to the effect of the strong CYP2C8 inhibitor gemfibrozil.7,8,9,10Clopidogrel, specifically its acyl‐β‐D‐glucuronide metabolite, has been discovered to inhibit CYP2C8, whereas prasugrel has not been studied in relation to its potential to interact with CYP2C8 substrates in humans.15,16,17To compare the effects of clopidogrel and prasugrel on CYP2C8 activity, we administered clopidogrel, prasugrel, or placebo together with montelukast. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein c4116e7c-72e1-11ee-ae93-0050569a1f61 10.1007/s00044-023-03089-9 There are a few noteworthy examples of metabolites inhibiting drug metabolizing enzymes wherein their corresponding parent drug did not have this effect (e.g., gemfibrozil glucuronide inactivation of CYP2C8; metabolites of bupropion and diltiazem inhibiting CYP2D6). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein 75165b84-3534-11e8-a51f-001a4a160176 21963058 Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein 1459199c-c8e6-11e5-9cb8-001a4ae51247 17670842 A recent report showed that the gemfibrozil glucuronide time-dependently inhibits CYP2C8 in vitro (Ogilvie et al., 2006). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P10632 Protein 96417de8-5ca4-11e7-af4d-001a4ae51247 26721703 The benzylic oxidation of the glucuronide by CYP2C8 leads to haem alkylation and irreversible inactivation of CYP2C8 (Baer et al., 2009;Jenkins et al., 2011). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein bb11c438-cb29-11e5-a6cd-001a4ae51247 11854149 Triacetyloleandomycin (an inhibitor of CYP3A4/5;Chang et al., 1994) and 13-cis-retinoic acid (an inhibitor of CYP2C8;Rahman et al., 1994;Baldwin et al., 1999) significantly inhibited the phosphonateO-deethylation of 4.4 μM NO-1886 to approximately 50% of the control values. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein 22da3f24-ca02-11e5-ab20-001a4ae51246 16176562 A glucuronide conjugate of gemfibrozil inhibits CYP2C8 more strongly than the parent compound does, which may explain at least some of its observed drug interactions (Shitaraet al. 2004). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein eba9a4c8-390c-11e8-9fbf-001a4a160176 27259818 In comparison to a recent clinical study where a profound interaction (an 8.3-fold AUC increase) was observed between repaglinide and gemfibrozil (via CYP2C8 inhibition by gemfibrozil acyl glucuronide) (Honkalammi et al., 2011), the above predicted value (a 3-fold AUC change) would represent a moderate interaction potential between repaglinide and SVAG even in the worst case scenario. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P10632 Protein e5fc19d6-c46d-11e5-9da3-001a4ae51247 PMC4152872 Dataset 2, gemfibrozil glucuronide inhibition of CYP2C8, also has a curved PRA plot. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y6L6 Protein 16745c8c-c98c-11ee-b346-0050569a791b 10.1016/j.biopha.2022.114078 Herein, we demonstrated that not only NAR, but also its sulfate and glucuronide conjugates can inhibit OATP1B1 and OATP2B1 function. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y6L6 Protein 796166e6-bc2f-11e5-ac4e-001a4ae51246 PMC2672446 Gemfibrozil and its glucuronide also inhibit OATP1B1. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y6L6 Protein a43c9746-c47c-11e5-a92e-001a4ae51246 21778352 "In addition, gemfibrozil and its glucuronide may competitively inhibit OATP1B1 and therefore interfere with repaglinide pharmacokinetics (Shitara et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y6L6 Protein 24b5f95a-84f3-11ee-add2-0050569a791b PMC9474414 Bempedoic acid and its glucuronide weakly inhibit OATP1B1 and OATP1B3 at clinically relevant concentrations, raising simvastatin blood levels3. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y6L6 Protein 75165b84-3534-11e8-a51f-001a4a160176 21963058 Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9Y6L6 Protein 22da3f24-ca02-11e5-ab20-001a4ae51246 16176562 The glucuronide conjugate of gemfibrozil inhibits, in addition to CYP2C8, also the uptake transporter organic anion transporting polypeptide 2 (OATP2, OATP1B1) (Shitaraet al.2004). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:Q96P20 Protein bfb26c00-5c31-11e7-8c5f-001a4ae51246 PMC5263152 In particular, treatment with wogonoside, a glucuronide metabolite of the bioactive flavonoid wogonin, reduced significantly colonic NF-κB and NLRP3 expression, as well as caspase-1 expression and activity in mice with colitis, exerting beneficial effects on colonic inflammation (69). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:O94956 Protein 16745c8c-c98c-11ee-b346-0050569a791b 10.1016/j.biopha.2022.114078 Herein, we demonstrated that not only NAR, but also its sulfate and glucuronide conjugates can inhibit OATP1B1 and OATP2B1 function. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P10415 Protein e15b9be8-bd8b-11ee-b7fc-0050569a1f61 10.1007/s12094-018-02011-9 In patients with recurrent SCLC, the addition to paclitaxel of INF-α plus modulation of BCL-2 by 13-cis-retinoic acid did not improve clinical outcomes in a single-arm phase II trial [35]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:P05121 Protein e815d5c8-3c6c-11f0-afc2-0050569a791b 10.1016/j.fct.2022.113254 Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P14410 Protein c8281e2c-c478-11e5-a92e-001a4ae51246 PMC3141883 "Likewise, kinetics of quercetin glucuronide isomer production in the medial and distal SI at 28 months were also better modeled by uncompetitive substrate inhibition." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q99626 Protein fd3bae24-bc37-11e5-ac4e-001a4ae51246 PMC3398007 We also showed that baicalin, a glucuronide-modified analogue of baicalein, is unable to induce Cdx2 and/or PXR and that it does not activate PXRin vitroorin vivo. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:O75762 Protein 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 This novel mechanism of ibuprofen/ibuprofen-acyl glucuronide indirectly underlines the TRPA1 contribution to acute nociception and delayed allodynia in various models of inflammatory pain. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases UNIPROT:P0CW71 Protein c2a79524-cce2-11ee-9aaa-0050569a1f61 10.1016/j.jff.2015.03.019 In cardiomyocytes, the monohydroxylated Uro B and its glucuronide, Uro B-gluc, reduced the levels of MCP-1 and VEGF, while the rest of the urolithins did not exert any effect. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P14635 Protein d3aa0a84-bbf5-11e5-9b9d-001a4ae51247 PMC3697306 One recent report from Vuletic and colleagues revealed that 13-cis-retinoic acid-treated HL-60 leukemia cells exhibited G0/G1 arrest and decreased cyclin B1 [23]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9NQ94 Protein 5a40da18-cbf1-11e5-b7d4-001a4ae51246 10069462 4-HPR, 13-cis-retinoic acid (RA) and all-trans-RA have been reported to reduce the yield of ACF induced by azoxymethane (AOM) in rats (20–23). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:Q9NQ94 Protein 94d4d04e-cb8d-11e5-9498-001a4ae51246 10837003 From the retinoid class, 4-hydroxyphenretinamide, all-transretinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid and retinol significantly inhibited ACF progression. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q8TDD2 Protein 0566eaaa-bbd9-11e5-8abe-001a4ae51246 10.1016/j.nutres.2012.09.018 Another study by the same group demonstrated that hesperetin-7-O-glucuronide, a form of conjugated glucuronide hesperidin, stimulated osteoblast differentiation by up-regulating mRNA gene expression (eg, ALP, Runx2, and osterix) and induced phosphorylation of Smad1/5/8 in primary rat osteoblasts[59]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q93070 Protein 0335bdba-dc3f-11ea-a28f-001a4a160175 PMC7260150 We have previously shown that BLEB attenuated changes in the cystometric parameters in a model of DO induced by administration of another retinoid, 13-cis-retinoic acid, in rats (Wróbel et al. 2019). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:O14709 Protein 0f7ee910-c955-11ee-9133-0050569a1f61 10.1016/j.jpba.2022.115115 The obtained results revealed that 1-Formyl-4-methoxy-β-carboline (P1), 1-Carboxylic acid-β-carboline (P2), hydroxylation and sulfate conjugation product of 1-Methoxicabony-β-carboline (P11-M2), hydroxylation and glucuronide conjugation product of 1-Methoxicabony-β-carboline (P11-M4), 1-Carbaldehyde-4,8-dimethoxy-β-carboline (P18), 1-β-Carboline-3-(4-methoxy-β-carboline)-propyl-2-one (P22) were key characteristic alkaloids-related prototype and their metabolites in control and colitis rats, the changed compounds, whose VIP > 1, |p(corr)| > 0.58, andpvalue < 0.5. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P02768 Protein 16745c8c-c98c-11ee-b346-0050569a791b 10.1016/j.biopha.2022.114078 Glucuronide conjugation of NAR strongly decreased the stability of albumin complexes, while the sulfate substitution led to a slight elevation in the binding affinity. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P05164 Protein dc326c66-3405-11e8-b868-001a4a160176 PMC5390522 Transformation of curcumin and its glucuronide by human leukocytes Freshly isolated human leukocytes were treated with PMA to activate myeloperoxidase prior to incubation with curcumin[27]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P0C2R8 Protein 542eb93e-3815-11e6-9aa8-001a4ae51247 25595597 "4B, the formation of 3-hydroxydesloratadine by CHHs was completely inhibited by montelukast, gemfibrozil, and gemfibrozil glucuronide, and was extensively inhibited by clopidogrel glucuronide (78.9%), repaglinide (73.3%), and cerivastatin (84.6%)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P0C2R8 Protein 542eb93e-3815-11e6-9aa8-001a4ae51247 25595597 "4B, the formation of 3-hydroxydesloratadine by CHHs was completely inhibited by montelukast, gemfibrozil, and gemfibrozil glucuronide, and was extensively inhibited by clopidogrel glucuronide (78.9%), repaglinide (73.3%), and cerivastatin (84.6%)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P04971 Protein c0b27ff0-72dc-11ee-ae93-0050569a1f61 PMC10471722 The resulting metabolites are sulfate or glucuronide conjugates of C20-reduced forms of BX. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:P05090 Protein 7a7d697a-5d75-11e6-9b08-001a4ae51246 10.1074/jbc.271.50.32105 In fact, we have found that all-trans-, 9-cis-, and 13-cis-retinoic acid strongly induce the expression of apoD in estrogen receptor-positive human breast cancer cells. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P08922 Protein 991b03b9-f540-11eb-bbe4-001a4a160176 29702430 Similar to indoles,p-cresyl sulfate andp-cresyl glucuronide induce ROS and are associated with cardiovascular and all-cause mortality [16,17,30,31]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:P08922 Protein 1980ad42-ae93-11ec-840e-0050569a791b PMCPMC8394930 Several flavonoid glucuronide derivatives at 1 μM inhibited NE release by 30–50% and at 10 μM, decreased ROS release by 50–70% from activated neutrophils [142]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P15559 Protein 6fbe4e54-bc04-11e5-9b9d-001a4ae51247 PMC3712174 Interestingly, as mentioned above, DMM, DMF, fish oil, 13-cis-retinoic acid, aspirin, and ibuprofen have been reported to upregulate NQO1 [26]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P61626 Protein fb35dc2c-bbff-11e5-8abe-001a4ae51246 10.1016/S0006-291X(03)00684-3 The attraction of the homogeneous enzyme immunoassay format for this purpose lies in the fact that anti-steroid glucuronide antibodies in the immune complex extensively inhibit the enzymic activity of steroid glucuronide conjugates of lysozyme. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P54136 Protein 3b31f977-dc77-11ea-8adc-001a4a160176 PMC6239946 ATRA and 13-cis-retinoic acid activates RARs, UAB30 primarily activates RXRs [15,19], and 9-cis-retinoic acid activate both [45]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:P54136 Protein d3fa81d6-bc0d-11e5-8abe-001a4ae51246 PMC3087887 Inhaled mid-dose isotretinoin (13-cis-retinoic acid) caused up-regulation of lung tissue nuclear RARs relative to vehicle-exposed mice [52]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q13950 Protein 0566eaaa-bbd9-11e5-8abe-001a4ae51246 10.1016/j.nutres.2012.09.018 Another study by the same group demonstrated that hesperetin-7-O-glucuronide, a form of conjugated glucuronide hesperidin, stimulated osteoblast differentiation by up-regulating mRNA gene expression (eg, ALP, Runx2, and osterix) and induced phosphorylation of Smad1/5/8 in primary rat osteoblasts[59]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits UNIPROT:P13521 Protein b5b7d61a-352d-11e8-87fd-001a4a160176 PMC5754284 Irinotecan is a semi‐synthetic prodrug that is metabolized by carboxylesterase to form the active metabolite SN‐38, which is subsequently metabolized in the liver by UGT1A1 to the inactive metabolite SN‐38 glucuronide (SN‐38G).21UGT1A1 is mainly expressed in the liver and is considered to be responsible for the inactivation of SN‐38, and genetic polymorphisms inUGT1A1result in reduced enzyme activity and increased irinotecan toxicity. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases UNIPROT:Q92911 Protein ef11d38e-bbe5-11e5-8abe-001a4ae51246 10.1016/j.cyto.2010.03.005 In experimental studies it has long been shown that 13-cis-retinoic acid (13-CRA) increases TSH-binding activity, NIS expression, and131I uptake[54,57,58]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates UNIPROT:Q5XLA6 Protein 80a3ceb8-c46c-11e5-85e4-001a4ae51246 24452863 To identify theO-glucuronide position of INCA, all possible glucuronide metabolites of INCA were synthesized by chemical synthesis. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:37386 Chemical 22f476a2-c916-11ee-b346-0050569a791b 10.1016/j.jpba.2022.115224 M59 and M109 were the glucuronide conjugate products of aurantio-obtusin or 1-desmethylobtusin. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:23965 Chemical 4d28701c-f543-11eb-bccc-001a4a160176 29466767 The binding of glucuronide in the liver accelerates estradiol clearance in the blood, resulting in inefficient accumulation in the target tissue [25]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:29917 Chemical baf145ba-c8df-11e5-9624-001a4ae51246 16540589 "The metabolic pathways identified for omapatrilat included methylation and disulfide conjugation at the free thiol group, glucuronide conjugation of the carboxyl group, oxidation of theS-methyl metabolite, and hydrolysis of the exocyclic amide bond." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:50730 Chemical 3bb0ac70-c478-11e5-85e4-001a4ae51246 21289076 "Of the six inhibitors selected for depletion studies, 8-methoxy-psoralen, gemfibrozil 1-O-β glucuronide, trimethoprim, ketoconazole, and troleandomycin inhibited the depletion rate of 0.02 μM montelukast by approximately 40 to 60%, whereas sulfaphenazole did not affect the depletion of montelukast at all (data not illustrated)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:50730 Chemical d9197b16-5cc2-11e7-8c5f-001a4ae51246 PMC4658491 Inhibition of Montelukast by Gemfibrozil and Its Glucuronide Metabolite in HLMs. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:38747 Chemical 16d23614-c72e-11ee-b346-0050569a791b 10.1016/j.fshw.2023.03.034 Taxifolin and its 5 main metabolites namely methylated taxifolin (Tax-CH3), methylated taxifolin sulfate (Tax-CH3-Sul), methylated taxifolin glucuronide (Tax-CH3-Glu), taxifolin glucuronide (Tax-Glu) and taxifolin sulfate (Tax-Slu) were found in rat plasma in the present study. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:39157 Chemical 0383d23c-c8e7-11e5-9cb8-001a4ae51247 17218485 TSA glucuronide,N-monodemethylated dinor dihydro trichostatic acid, andN-didemethylated TSA amide were among the major metabolites after 24 h of exposure (Table 3). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:23053 Chemical ed2a291c-3533-11e8-9fbf-001a4a160176 21371557 EGC glucuronide, methylated EGC glucuronide, methylated EGC sulfate, EC glucuronide, EC sulfate, methylated EC sulfate, as well as the glucuronide and sulfate metabolites of the ring fission metabolites of tea catechins, M4, M6 and M6′, were the major human urinary metabolites of tea polyphenols. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:8988 Chemical 03adc30a-c467-11e5-85e4-001a4ae51246 24346835 "Biliary excretion of SN-38 and glucuronide via MRP2, with subsequent enterohepatic cycling, contributes to enterocyte SN-38 exposure." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:8988 Chemical af84219a-c8e7-11e5-a1fd-001a4ae51246 17577039 "SN-38 biliary excretion is enhanced by the formation of SN-38 glucuronide (SN-38G), which is catalyzed primarily by the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1).13 UGT1A1 catalyzes transfer of a glucuronic acid moiety from the cofactor uridine diphosphoglucuronic acid (UDPGA) to bilirubin and insoluble xenobiotics (eg, SN-38)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:8988 Chemical 1646e838-bc2f-11e5-ac4e-001a4ae51246 PMC2361767 Cleavage by carboxylesterase yields the active metabolite SN-38, which is inactivated by glucuronide conjugation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) (Haaz et al, 1997), variable activity of which is a determinant of toxicity (Innocenti et al, 2004). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:8988 Chemical f78822ba-c8de-11e5-a1fd-001a4ae51246 16985062 "Secondly, it is thought that bacteria in the gut that have glucuronidase activity can hydrolyze the SN-38 glucuronide to produce SN-38 (33,34)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:28777 Chemical 55e45e7c-f588-11eb-8b14-001a4a160175 30870692 These metabolites were licochalcone A glucuronide (M3), daidzein-O-glucuronide(M4), demethylated nobiletin(M6), diosmetin-O-sulfate(M11), naringin-O-glucuronide(M13), astilbin glucuronide(M14), liquiritigenin-O-glucuronide(M16), methylated and hydroxylated naringenin(M19), methylated liquiritigenin(M23), catechin glucuronide(M26) and hesperidin-O-glucuronide(M28). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:48526 Chemical 21aaaf98-720c-11ee-ae93-0050569a1f61 10.1007/s00044-023-03144-5 8Metabolic activation of 2-phenylpropionic acid (2-PPA) by acyl-CoA thioester formation and acyl glucuronide formation followed by reaction with glutathione (GSH) leading to 2-PPA-GSH thioester formation Additionally, the ability of 2-PPA-acyl-CoA to transacylate bovine serum albumin (BSA) was shown from incubations in buffer where radiolabeled [1,2-14C2]-2-PPA reacted covalently with the protein primarily forming ester and amide-linked adducts [36]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:25696 Chemical 416ba284-ae94-11ec-8f68-0050569a1f61 PMC8266788 Bempedoic acid and its glucuronide also weakly inhibit the organic anion transporting polypeptides (OATPs) 1B1 and OATP1B3, which typically transport large hydrophobic organic anions [25], at clinically relevant concentrations, and also weakly inhibit OAT2 in vitro. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:25696 Chemical 1459199c-c8e6-11e5-9cb8-001a4ae51247 17670842 "In addition, gemfibrozil and its glucuronide are indicated to inhibit organic anion transporting polypeptide 1B1 (Shitara et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:25696 Chemical 9b29aeb0-c471-11e5-91a7-001a4ae51247 19773535 "In addition to inhibiting CYP2C8, gemfibrozil and/or its glucuronide can competitively inhibit some other P450 enzymes and organic anion-transporting polypeptide (OATP) 1B1 in vitro (Wen et al., 2001;Shitara et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:36281 Chemical 088c9277-f53b-11eb-ba39-001a4a160176 29655093 Moreover,33/34were produced by methylation and glucuronide of caffeic acid [28]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:36281 Chemical b4aa534a-f58e-11eb-8d5c-001a4a160175 30172880 While the metabolite M4-5m/z369.0817 was 176 Da higher than methylated caffeic acid, indicating M4-5 was glucuronide conjugation. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:17256 Chemical 5f863140-c46b-11e5-a92e-001a4ae51246 25142735 The MS2product spectrum of M14 showed a characteristic glucuronide loss of 176 Da to yield product ion atm/z342.1084, which is the molecular mass of M3. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:17256 Chemical 4e67c892-cb28-11e5-8189-001a4ae51246 11302928 "Using capillary HPLC/CF-LSIMS in full-scan mode, the biosyntheticp-OH-DFU glucuronide produced an abundant MNH4+ion at 570 Da, but no corresponding molecular ion at 570 Da was visible in the spectrum of metabolite M1 from the hepatocyte mixture." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:17256 Chemical 55e5bbc5-f58a-11eb-8bcd-001a4a160175 30590334 In all cases, apigenin was observed atm/z269, and the attached sugars were glucuronide moieties (neutral losses of 176 Da). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:17256 Chemical c9ccab88-d6b8-11e5-8dc2-001a4ae51247 9862787 "The facile loss of the glucuronide moiety (loss of 176 Da) during collisional activation did not allow determination of the position of glucuronidation, but this neutral ion loss is quite indicative of the presence of a glucuronic acid conjugate (Straub et al., 1987)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:28870 Chemical 13765aa4-cb29-11e5-8189-001a4ae51246 11408365 "A species difference in biliary metabolite profile existed in that bexarotene acyl glucuronide was the predominant metabolite in rat, while in dog the major metabolite was hydroxylated bexarotene acyl glucuronide." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:28870 Chemical ed2a291c-3533-11e8-9fbf-001a4a160176 21371557 EGC glucuronide, methylated EGC glucuronide, methylated EGC sulfate, EC glucuronide, EC sulfate, methylated EC sulfate, as well as the glucuronide and sulfate metabolites of the ring fission metabolites of tea catechins, M4, M6 and M6′, were the major human urinary metabolites of tea polyphenols. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:28870 Chemical 730f1ace-bc3c-11e5-9b9d-001a4ae51247 PMC4055232 Extracted ion chromatograms (EICs) ofm/z283.1540 for QHS and monohydroxylated deoxy-QHS,m/z284.1856 for deoxy-QHS,m/z316.1775 for monohydroxylated QHS,m/z332.1704 for dihydroxylated QHS,m/z476.2126 for the glucuronide of monohydroxylated deoxy-QHS,m/z492.2076 for the glucuronide of monohydroxylated QHS, andm/z316.2118 for ARM (the internal standard; IS), with a 5 ppm range centred on the exactm/zvalue were generated for quantitation. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:28870 Chemical 1e3d7554-d049-11ec-99c8-0050569a791b PMC8577747 It is mostly hydroxylation of the 2-methyl group (2-hydroxymetronidazole), oxidation of the 1-ethyl group (1-metronidazole acetic acid) and glucuronide conjugation of hydroxylated metabolite (metronidazole glucuronide) (Fig 1). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:28870 Chemical 3d30b014-3522-11e8-8f56-001a4a160175 23835414 Phase II metabolites of ibuprofen The ion peak attR16.0min gave am/zof 381.1556 (peak 4), which corresponds to the mass of acyl glucuronide of IBF, while them/z397.1512±0.0001 recorded for the peaks eluting attR10.0–11.9min (peaks marked with 5) and at peak attR1.6min (peak 6) corresponded to the mass of the acyl glucuronide of hydroxylated IBF or ether glucuronide of hydroxylated IBF. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:28870 Chemical 1d57c780-377c-11e8-87fd-001a4a160176 19362796 The fragment ion atm/z374 (374=198+176) was the glucuronide conjugated benzoyl moiety and it further produced the ions atm/z198 and 170 by losses of glucuronide and CO, respectively. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:47344 Chemical 615e81cc-c47d-11e5-85e4-001a4ae51246 PMC2895033 Drug-drug interactions would not be expected with loperamide and flavopiridol, which is eliminated primarily by glucuronidation and biliary excretion of both parent and glucuronide metabolites.38–41Additionally, our flavo-G data do not support the latter hypothesis, as we saw no indication of upregulation of UGT activity between days 1 and 3 (data not shown). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:15841 Chemical 1459199c-c8e6-11e5-9cb8-001a4ae51247 17670842 "In addition, gemfibrozil and its glucuronide are indicated to inhibit organic anion transporting polypeptide 1B1 (Shitara et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:15841 Chemical 9b29aeb0-c471-11e5-91a7-001a4ae51247 19773535 "In addition to inhibiting CYP2C8, gemfibrozil and/or its glucuronide can competitively inhibit some other P450 enzymes and organic anion-transporting polypeptide (OATP) 1B1 in vitro (Wen et al., 2001;Shitara et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:15841 Chemical 22da3f24-ca02-11e5-ab20-001a4ae51246 16176562 The glucuronide conjugate of gemfibrozil inhibits, in addition to CYP2C8, also the uptake transporter organic anion transporting polypeptide 2 (OATP2, OATP1B1) (Shitaraet al.2004). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:9584 Chemical a1656ce6-340a-11e8-87fd-001a4a160176 27395336 Moreover, PFCs may inhibit the expression of sulfate conjugation and the glucuronide conjugation pathway, which reduces the biliary excretion of thyroid hormones (Liu et al., 2011). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:6087 Chemical 8d1abec6-8470-11e9-bf76-001a4a160175 PMC6572607 The product ion at m/z 338.1459 was produced by the loss of a glucuronide group to form the corresponding aglycon (jatrorrhizine or columbamine). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:26333 Chemical 161c8694-cbf0-11e5-83a8-001a4ae51246 10024618 "This prostaglandin-lowering possibility of aglycone and glucuronide isoflavones might be especially helpful for elderly people whose NK activity is decreased and prostaglandin production increased with age (Meydani et al. 1988)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:24297 Chemical da0d689e-bbf5-11e5-9b9d-001a4ae51247 PMC3818846 The low level of glucuronide metabolites implies that energy metabolism decreased and the energy metabolism pathway increased, resulting in abnormal pentose and glucuronate interconversions. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:31597 Chemical 08028336-3aa4-11e8-8636-001a4a160175 25706568 The data allowed us to deduce that M2was the glucuronide conjugative product of felbinac and the mostly likely structure (glucuronide felbinac) was proposed. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:25698 Chemical 3d30b014-3522-11e8-8f56-001a4a160175 23835414 Phase II metabolites of ibuprofen The ion peak attR16.0min gave am/zof 381.1556 (peak 4), which corresponds to the mass of acyl glucuronide of IBF, while them/z397.1512±0.0001 recorded for the peaks eluting attR10.0–11.9min (peaks marked with 5) and at peak attR1.6min (peak 6) corresponded to the mass of the acyl glucuronide of hydroxylated IBF or ether glucuronide of hydroxylated IBF. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:17474 Chemical 98d8fc6a-bc4c-11e5-9b9d-001a4ae51247 PMC3894546 In contrast, glucuronide conjugate showed little or no inhibitory effect on the OAT4-mediated transport of estrone sulfate. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:17474 Chemical e5950d0e-cb89-11e5-8106-001a4ae51247 10660625 By contrast, glucuronide conjugates showed little or no inhibitory effect on the OAT4-mediated transport of estrone sulfate. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:24298 Chemical 09c0ec53-f541-11eb-ae7f-001a4a160175 29986279 UDP-glucuronosyltransferases (UGTs) catalyze the covalent linkage of glucuronic acid to some hydrophobic parent compounds and intermediate metabolites transformed by CYP450 enzymes in phase I. Afforded by higher solubility and polarity, glucuronide conjugates are easily eliminated from the cell to reduce the serious injury of oxidative stress (Torres et al., 2008). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:132853 Chemical 02016d0a-bc1e-11e5-9b9d-001a4ae51247 10.1016/j.jchromb.2013.09.023 A series ofM14 (M14a–f)andM15 (M15a–f)metabolites showed the same predominant quasi-molecular ion atm/z813.2449 (C36H45O21) and 827.2612 (C37H47O21), respectively.M14sandM15swere both 176Da heavier thanM12sandM13s, suggesting that they were successive glucuronide conjugate products of mono- and dimethyl acteoside. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:9017 Chemical 55e45e7c-f588-11eb-8b14-001a4a160175 30870692 They were danshensu (M1), salvianolic acid B glucuronide (M9), methylated salvianolic acid A (M17), hydrolysate of salvianolic acid B (M20) and rosmarinic acid glucuronide (M21). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:8805 Chemical 60b306fa-c485-11e5-a92e-001a4ae51246 22451699 "The fraction metabolized via CYP2C8 estimated in this study was <50% and would not account for the observed increase in repaglinide AUC caused by gemfibrozil and its glucuronide, strongly indicating that inhibition of repaglinide uptake into the cell in addition to irreversible inhibition of CYP2C8 needs to be considered." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 methylatesProtein CHEBI:50202 Chemical 55e45e7c-f588-11eb-8b14-001a4a160175 30870692 These metabolites were licochalcone A glucuronide (M3), daidzein-O-glucuronide(M4), demethylated nobiletin(M6), diosmetin-O-sulfate(M11), naringin-O-glucuronide(M13), astilbin glucuronide(M14), liquiritigenin-O-glucuronide(M16), methylated and hydroxylated naringenin(M19), methylated liquiritigenin(M23), catechin glucuronide(M26) and hesperidin-O-glucuronide(M28). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:132050 Chemical 7a180632-c470-11e5-85e4-001a4ae51246 19687151 It is also possible that there are some glucuronide products of norverapamil. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:68583 Chemical 468ace28-d48b-11e5-a1eb-001a4ae51246 25384899 "Minor metabolites identified in rat and dog excreta included an acyl glucuronide (M1), two monohydroxylated regioisomers (M2aand M2b), and 6-aminonicotinic acid (M3)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:78509 Chemical 3106fd46-3759-11e8-87fd-001a4a160176 27163969 Vogeser et al.[76]showed that in-source fragmentation of the main metabolite of mycophenolic acid (MPA), a phenolic glucuronide, to MPA may cause erroneously high MPA concentrations in clinical samples if not separated chromatographically. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:78509 Chemical 661c3fcc-ca01-11e5-be63-001a4ae51246 16272406 "Similarly, although Hesselink et al. (2005) suggest that CsA inhibits the enterohepatic recirculation of MPA, they did not measure the total recovery of MPA and its glucuronide metabolites in bile and, thus, could not distinguish between an effect of CsA on the biliary secretion of the glucuronide metabolites and their hydrolysis in the gut." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:78509 Chemical e4a56d9a-cb29-11e5-b419-001a4ae51246 11856782 "The pharmacologically inactive phenolic glucuronide metabolite of MPA, MPAG, competes for the albumin binding sites and can increase the fraction of unbound active MPA when present at high concentrations, for example as a consequence of renal failure (5,19)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:23240 Chemical 498bd632-c8e0-11e5-9ad8-001a4ae51247 PMC4106413 Prolonged inhibition of the chromophore production by 13-cis-retinoic acid protected rats from light damage (Sieving et al., 2001). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:82960 Chemical 10539d2e-bc1e-11e5-8abe-001a4ae51246 10.1016/j.jchromb.2009.02.057 Interestingly, our method enables the simultaneous determination of raltegravir–glucuronide, giving some insight into the role of the UGT1A1-mediated metabolism of raltegravir. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:16189 Chemical da680bf0-c47e-11e5-85e4-001a4ae51246 20089784 The efflux oftrans-resveratrol glucuronide was inhibited by 55% (P< 0.05) and that of the sulfate by 28% (P< 0.05). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:8764 Chemical d085e574-865e-11e6-81bd-001a4ae51246 PMC5030415 The exact mechanism of this action is not known but some of the postulates are the blocking ofde novopurine synthesis in enterocytes, acyl glucuronide metabolite induced toxicity, and antibacterial effect of MMF [4,7–9]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:39867 Chemical 2867acf6-686b-11e8-8329-001a4a160176 PMC5939412 Increased renal clearance,1reduced intestinal VPA absorption,2increased VPA glucuronidation,1increased distribution of VPA into erythrocytes, decreased hydrolysis of VPA glucuronide (VPA‐G) to VPA,3and inhibition of plasma protein binding of VPA4were implicated. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:60285 Chemical 2041aa6c-c91e-11ee-b346-0050569a791b 10.1016/j.jep.2022.115866 They were glucuronide products of DOPE type.M47was a hydroxylated mono-glucuronide metabolite product. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:33364 Chemical 97d4a4ce-bbf0-11e5-8abe-001a4ae51246 10.1016/j.bmcl.2004.06.015 The attachment of a glucuronide unit to a platinum derivative greatly enhances the solubility of the platinum compound in aqueous media and probably leads to a reduced cell-membrane permeability of the prodrug. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases CHEBI:15724 Chemical c853a036-bc41-11e5-9b9d-001a4ae51247 10.1016/j.ijpara.2009.11.003 As the co-infection progressed to week 5 p.i., additional variations in metabolite composition were noted; decreased levels of betaine and TMAO with increased levels of 4-cresol glucuronide and PAG were observed in urine from infected hamsters. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:37136 Chemical 4cbabe46-340d-11e8-a34b-001a4a160175 24378615 Approximately 60% of oral dose is absorbed, but pre-systemic glucuronide conjugation is extensive, which limits its oral BA[6]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:7889 Chemical 063d0d0e-0e4a-11e8-8970-001a4a160176 PMC5761054 Thus M11 was tentatively identified as glucuronide conjugate of hydroxylated isomer of paeoniflorin. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein CHEBI:16898 Chemical 21762a52-3531-11e8-a34b-001a4a160175 24631812 For instance, research on the metabolism of azimsulfuron in rats, a sulfonylurea herbicide used for rice weeds, revealed that O-demethylation was the major metabolic pathway, and other minor pathways included the hydroxylation of the pyrimidine ring, cleavage of the sulfonylurea linkage, and glucuronide and sulfate conjugation of the hydroxylated metabolites[13]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:28197 Chemical b2c9a26e-c7ba-11ee-9133-0050569a1f61 10.1016/j.jff.2023.105654 Daidzein will be converted to glucuronide or sulfate (RHuang et al., 2013) and soy extract consumption stimulated the formation of daidzein sulfoglucuronide, glucuronide, and sulfate (Soukup et al., 2016). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates CHEBI:68647 Chemical 959dbbb0-ac41-11ee-a19b-0050569a791b PMC7434894 Regorafenib combined with 13-cis-retinoic acid is effective against neuroblastoma cells and induces changes in intracellular signalling pathway expression and activity We have previously shown that the combination of RET inhibition with 13-cis-retinoic acid, a vitamin A analogue currently used for maintenance therapy in children with neuroblastoma,35demonstrated synergistic efficacy against neuroblastoma in preclinical models.29,36To determine whether 13-cis-retinoic acid also enhanced the efficacy of regorafenib, neuroblastoma cell lines were treated with regorafenib alone and in combination with 13-cis-retinoic acid. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits CHEBI:15920 Chemical 8d1abec6-8470-11e9-bf76-001a4a160175 PMC6572607 The product ion at m/z 338.1459 was produced by the loss of a glucuronide group to form the corresponding aglycon (jatrorrhizine or columbamine). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D005978 Phenotype f07e663c-81b8-11ee-add2-0050569a791b 10.1007/s12011-022-03114-9 In chronic use or high doses, the glucuronide and sulfate conjugation pathways reach saturation and this causes glutathione depletion which gives rise to the accumulation of toxic NAPQI and p-aminophenol metabolites. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D005978 Phenotype 1d42258a-ca5d-11e5-a3f7-001a4ae51246 12893835 "Interestingly, both steroid glucuronide conjugates decreased the biliary concentration of glutathione, which was slightly more pronounced in the E2-17G group at later times (Fig. 3B)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006810 Phenotype a9c687b6-c8e7-11e5-9cb8-001a4ae51247 17578901 "Because NSAIDs are mainly excreted into the urine as the glucuronide-conjugated form (Davies and Anderson,1997a,b), we evaluated the inhibitory effect of diclofenac and naproxen glucuronide, which were prepared biosynthetically in vitro, on MRP2-mediated transport of MTX (Fig. 5E)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006810 Phenotype acf02b3a-c8e8-11e5-9ad8-001a4ae51247 17656469 "Recently, Luo et al. (2007) have reported that DPC 333 may be a substrate for P-glycoprotein and that glucuronide conjugates of DPC 333 may inhibit the Mrp-2-mediated transport of methotrexate." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006810 Phenotype 513c0ee6-c468-11e5-91a7-001a4ae51247 PMC3629805 "Although the role of MRP1 (ABCC1) specifically in R3G transport has not been evaluated, there are reports of MRP1-mediated transport of glucuronides such as 17β-estradiol-glucuronide (Jedlitschky et al., 1996), etoposide glucuronides, SN-38 glucuronide (Deeley and Cole, 2006), andβ-O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) (Leslie et al., 2001)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006810 Phenotype 98d8fc6a-bc4c-11e5-9b9d-001a4ae51247 PMC3894546 In contrast, glucuronide conjugate showed little or no inhibitory effect on the OAT4-mediated transport of estrone sulfate. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006810 Phenotype e5950d0e-cb89-11e5-8106-001a4ae51247 10660625 By contrast, glucuronide conjugates showed little or no inhibitory effect on the OAT4-mediated transport of estrone sulfate. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D002779 Phenotype c9ae947c-c8df-11e5-9624-001a4ae51246 16554370 "Indeed, this and other D-ring glucuronide conjugates such as estradiol 17β-glucuronide induce acute cholestasis (Meyers et al., 1980;Vore, 1987)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0050817 Phenotype 9c8a9938-bc4a-11e5-ac4e-001a4ae51246 10.1016/j.ejphar.2011.10.009 Darexaban and darexaban glucuronide inhibited plasma coagulation in several species, and were most effective in human plasma. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D008550 Phenotype c536f200-bc18-11e5-9b9d-001a4ae51247 PMC3968369 Two other metabolic pathways of tryptophan metabolism are also described: the serotonin pathway that leads to melatonin, and the indolic pathway that leads to indolic components such as indoxyl sulfate (IS), indole acetic acid (IAA), and indoxyl-β-D glucuronide (IDG) (Figure 1) [7,11,12]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein MESH:D008795 Phenotype 1e3d7554-d049-11ec-99c8-0050569a791b PMC8577747 It is mostly hydroxylation of the 2-methyl group (2-hydroxymetronidazole), oxidation of the 1-ethyl group (1-metronidazole acetic acid) and glucuronide conjugation of hydroxylated metabolite (metronidazole glucuronide) (Fig 1). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009173 Phenotype efe28868-c46d-11e5-9da3-001a4ae51247 PMC4152871 "In fact, inhibition of hepatic uptake and biliary excretion of mycophenolic acid glucuronide, which disrupts enterohepatic recirculation of the parent mycophenolic acid, is postulated as the mechanism behind decreased systemic exposure to mycophenolic acid during coadministration with cyclosporine in transplant patients (Pou et al., 2001;Matsunaga et al., 2014)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D059808 Phenotype 50365576-c944-11ee-9133-0050569a1f61 10.1016/j.jnutbio.2022.109219 Synthesis and purification of lignan glucuronides ED glucuronide (EDGlu) was synthesized using a polyphenol conjugation protocol [28,29]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D020927 Phenotype bbb0065c-cb29-11e5-b419-001a4ae51246 11854148 "Unlike with human liver microsomes, only one glucuronide product of dexmedetomidine (, 7.7 min) was detected (Fig.2b)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases MESH:D006626 Phenotype c853a036-bc41-11e5-9b9d-001a4ae51247 10.1016/j.ijpara.2009.11.003 Among these altered gut-microbiotal-related metabolites, the decreased level of hippurate and increased levels of 4-cresol glucuronide and PAG appeared to be common to all helminth infections studied to date (Wang et al., 2004, 2006, 2009; Saric et al., 2008, 2009). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0032637 Phenotype 541378dc-bc31-11e5-9b9d-001a4ae51247 10.1016/j.abb.2008.01.019 Nevertheless, it is not excluded that the failure of the glucuronide conjugates to inhibit IL-8 production by HaCaT cells following UV irradiation could be due to the absence of the transporter involved in the uptake of the glucuronides on HaCaT cells or on keratinocytes in general. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009020 Phenotype 70db29f6-c99d-11ee-b346-0050569a791b 10.1016/j.canlet.2022.215969 In these peptides, a glucuronide is added to the 6-hydroxy group of M6G, increasing the hydrophilicity and polarity of morphine and facilitating its excretion in urine [97]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D006863 Phenotype 798f9370-bc45-11e5-8abe-001a4ae51246 10.1016/S0378-4347(01)00177-3 The hydrolysis of acyl glucuronide reforming the parent drug in plasma samples can be significantly reduced by lowering the pH to 5.0. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D013928 Phenotype 6e6b3c92-375e-11e8-a34b-001a4a160175 24462050 The glucuronide forms of RSV, with a m/z at 403 were fragmented using a collision induced dissociation (CID) equal to 16 (arbitrary units), whereas sulfate conjugates (m/z 307) required a CID of 23 and then free RSV was further fragmented with a CID of 34. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D002294 Phenotype c6915fc0-cb8e-11e5-984a-001a4ae51247 10716952 "When combined with interferon α2A, 13-cis-retinoic acid causes complete and partial remissions of squamous cell carcinomas of the skin and cervix." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D005910 Phenotype f25719da-aa75-11e6-bcbe-001a4ae51246 PMC5349921 Moreover, the combination of IFN-α and 13-cis-retinoic acid enhanced glioma susceptibility to IRin vitrobut did not result in a better outcome in patients treated with IR plus IFN-α as compared to IR alone [47]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D013256 Phenotype fb35dc2c-bbff-11e5-8abe-001a4ae51246 10.1016/S0006-291X(03)00684-3 The attraction of the homogeneous enzyme immunoassay format for this purpose lies in the fact that anti-steroid glucuronide antibodies in the immune complex extensively inhibit the enzymic activity of steroid glucuronide conjugates of lysozyme. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0002524 Phenotype a41de36e-f53f-11eb-ae0f-001a4a160175 29501520 In particular, the reduction in glucuronide conjugation in young infants and the faster rates of cytochrome P450 (CYP)-mediated reactions in infants and children compared with adults may result in increased production of reactive metabolites and increased susceptibility of hypersensitivity reactions in children. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D015458 Phenotype f922bd16-cc75-11e5-aade-001a4ae51247 9354458 We have shown that cell cycle progression of human T-cell leukemia virus type I (HTLV-I)-transformed T-cell lines was inhibited by 13-cis-retinoic acid (13cRA). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D000077195 Phenotype 87396f7e-ccfc-11e5-b6ad-001a4ae51246 8625298 In this study, we have evaluated whether IFN-alpha-2a and/or 13-cis-retinoic acid (RA) enhance radiation cytotoxicity in a head and neck squamous cell carcinoma cell line (FaDu). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D010429 Phenotype da0d689e-bbf5-11e5-9b9d-001a4ae51247 PMC3818846 The low level of glucuronide metabolites implies that energy metabolism decreased and the energy metabolism pathway increased, resulting in abnormal pentose and glucuronate interconversions. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D007971 Phenotype 334d51f4-c465-11e5-9da3-001a4ae51247 PMC3773490 "In prevention, 13-cis-retinoic acid decreased leukoplakia lesion size in 67% of patients compared to 10% in placebo and reversed dysplasia in 54% of patients compared to 10% in the placebo group (76)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0010467 Phenotype e6f9cd5c-a5c5-11e7-8112-001a4a160175 PMC5617156 RSV and the glucuronide metabolites increased miR-155 gene expression, but 3S metabolite did not (Fig 1A). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0010467 Phenotype 0566eaaa-bbd9-11e5-8abe-001a4ae51246 10.1016/j.nutres.2012.09.018 Another study by the same group demonstrated that hesperetin-7-O-glucuronide, a form of conjugated glucuronide hesperidin, stimulated osteoblast differentiation by up-regulating mRNA gene expression (eg, ALP, Runx2, and osterix) and induced phosphorylation of Smad1/5/8 in primary rat osteoblasts[59]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0009058 Phenotype 89548b18-c7c6-11ee-9133-0050569a1f61 10.1016/j.fbio.2023.102866 RSV and Glucuronide resveratrol (GRSV) its main metabolite can reduce hepatic cholesterol increasing the synthesis and efflux of bile acids and decreasing the synthesis and increasing cholesterol efflux. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0009058 Phenotype d085e574-865e-11e6-81bd-001a4ae51246 PMC5030415 The exact mechanism of this action is not known but some of the postulates are the blocking ofde novopurine synthesis in enterocytes, acyl glucuronide metabolite induced toxicity, and antibacterial effect of MMF [4,7–9]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0009058 Phenotype 238369d0-c6b3-11ee-9aaa-0050569a1f61 10.1016/j.lfs.2023.122243 Its biosynthesis is produced by the stereospecific enzymaticco-polymerization ofN-acetylglucosamine and glucuronide, a reaction process in which hyaluronate synthase requires UDP-N-acetylglucosamine and UDP-glucuronide as sugar donors to produce approximately 1 million Dalton units of polymer in one minute. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0009058 Phenotype 44eace18-ab92-11e6-9ac8-001a4ae51246 PMC4613946 A lack of commercially available glucuronide standards necessitates chemoenzymatic synthesis and purification of glucuronide metabolites for analytical development and application. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0009058 Phenotype 89548b18-c7c6-11ee-9133-0050569a1f61 10.1016/j.fbio.2023.102866 RSV and Glucuronide resveratrol (GRSV) its main metabolite can reduce hepatic cholesterol increasing the synthesis and efflux of bile acids and decreasing the synthesis and increasing cholesterol efflux. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D006930 Phenotype 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 Ibuprofen-acyl glucuronide reduces TRPA1-dependent hyperalgesia and nociception in models of inflammatory pain We tested the ability of ibuprofen-acyl glucuronide to reduce mechanical allodynia evoked by intraplantar carrageenan injection in the mouse hind paw. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D014839 Phenotype b61f9e76-3532-11e8-8f56-001a4a160175 24161560 Moreover, arvanil, a synthetic agonist of CB1 and TRPV1receptors, alleviate emesis induced by morphine 6 glucuronide in the ferrets (Sharkey et al., 2007). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008283 Phenotype 66ae8f8c-ca5e-11e5-a3f7-001a4ae51246 12660332 In proliferating renal diseases, exogenous administration of ATRA, 9-cis-retinoic acid, or 13-cis-retinoic acid suppresses the proliferation of mesangial cells (26,27⇓). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008283 Phenotype 05479fc0-c46b-11e5-91a7-001a4ae51247 25102117 Meyskens and Fuller [134] found that 13-cis-retinoic acid, retinol and β-all-trans-retinoic acid were able to inhibit proliferation in human melanoma cellsin vitro, which fueled further studies on the use of retinol and related agents as possible anti-cancer compounds in melanoma. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008283 Phenotype aa8bd7d4-352b-11e8-9192-001a4a160175 27832522 Retinoids, including all trans-retinoic acid (ATRA) and 13-cis-retinoic acid (13-cis-RA), inhibit the proliferation and stimulate differentiation of NB cells [5,6]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009369 Phenotype 3e566bc2-c473-11e5-9cc6-001a4ae51246 PMC2733247 "The sample of patients in the Wu et al. analysis had histologically confirmed stage I or II head and neck squamous cell carcinoma and participated in the Retinoid Head and Neck Second Primary Trial, a randomized, placebo-controlled chemoprevention trial of daily low-dose 13-cis-retinoic acid in preventing second primary tumors over several years (6)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009369 Phenotype 5b9f1bd6-c471-11e5-85e4-001a4ae51246 19138978 "In patients with a history of SCCHN, chemoprevention with high-dose 13-cis-retinoic acid reduced the recurrence rate of OPLs and decreased the risk of second primary tumors (14)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009369 Phenotype 2bf32356-3917-11e8-8f56-001a4a160175 24480360 Thus, by combining a low toxicity and a selective activation in the tumor microenvironment, glucuronide prodrugs allow the increased drug deposition in the tumor while reducing drug concentration in normal tissues. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009369 Phenotype 5be6bb30-ca02-11e5-9b70-001a4ae51247 16174848 Some of the most compelling evidence of a chemopreventive agent–smoking interaction comes from the Lung Intergroup Trial(17), a randomized, placebo-controlled phase III trial of the retinoid 13-cis-retinoic acid (13cRA) in preventing second primary tumors in definitively resected early-stage lung cancer patients. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009369 Phenotype 9c8075e6-c9fd-11e5-be63-001a4ae51246 14871993 "In clinical trials, 13-cis-retinoic acid has been shown to suppress or reverse epithelial carcinogenesis and to prevent second primary tumors in patients with SCC(4, 5)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009369 Phenotype 3e5ce8b2-c473-11e5-91a7-001a4ae51247 PMC2964280 "Materials and Methods Study population and epidemiologic data The subjects included in this study were participants enrolled (1991-1999) in the Retinoid Head and Neck Second Primary Trial designed to evaluate whether daily low-dose 13-cis-retinoic acid (13-cRA) prevents SPT or tumor recurrence in early-stage HNSCC patients (1)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009369 Phenotype 3937d8e0-c47f-11e5-a92e-001a4ae51246 PMC3182269 In conclusion, our data indicate that overlapping treatments with 13-cis-retinoic acid and cytotoxic agents could diminish tumor response to cytotoxic drugs. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009369 Phenotype c7c1e118-bc10-11e5-8abe-001a4ae51246 PMC3780469 The retinoid 13-cis-retinoic acid was shown to reduce the incidence of second primary tumors; however, it has not been used clinically for prevention because of its toxicity. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009369 Phenotype 23d27ee8-c474-11e5-9cc6-001a4ae51246 26284997 Hong and colleagues reported that 1 year of high-dose 13-cis-retinoic acid (13-cRA) significantly reduced the incidence of second primary tumors (SPTs) in patients with curatively treated stage I through IV head and neck squamous cell carcinoma. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0051320 Phenotype 073f94ee-cb8d-11e5-984a-001a4ae51247 10626810 In fact, NDGA and 13-cis-retinoic acid produced an S-phase block with a higher percentage of cells in the S phase. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0051320 Phenotype 073f94ee-cb8d-11e5-984a-001a4ae51247 10626810 In fact, NDGA and 13-cis-retinoic acid produced an S-phase block with a higher percentage of cells in the S phase. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases MESH:D002784 Phenotype 2930e234-bc37-11e5-8abe-001a4ae51246 PMC3071816 The ability of naringenin, and its glucuronide metabolites, to reduce plasma cholesterol levels has been demonstratedin vivo[10],[11],[12], while its ability to reduce ApoB secretion has been demonstrated extensivelyin vitro[13],[14]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002784 Phenotype 89548b18-c7c6-11ee-9133-0050569a1f61 10.1016/j.fbio.2023.102866 RSV and Glucuronide resveratrol (GRSV) its main metabolite can reduce hepatic cholesterol increasing the synthesis and efflux of bile acids and decreasing the synthesis and increasing cholesterol efflux. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002784 Phenotype 0513222a-bc39-11e5-ac4e-001a4ae51246 PMC3252497 Ezetimibe glucuronide is then excreted into the gut, localizes at the brush border of the small intestine, and inhibits the absorption of ingested cholesterol by about 50% [13]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002784 Phenotype 4efee8a8-3534-11e8-9192-001a4a160175 21798251 Cell pre-treatment with the glucuronide metabolites significantly inhibited the formation of MDA and fatty acid and cholesterol major oxidation products, HP and 7-keto. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002784 Phenotype 77e50660-3919-11e8-87fd-001a4a160176 21291801 Colesevelam HCl is an effective and well-tolerated non-absorbed bile acid sequestrant, whereas ezetimibe, a 2-azetidinone, and its active metabolite, ezetimibe glucuronide, inhibit cholesterol absorption in the small intestine. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D012176 Phenotype ef16a7f4-352f-11e8-a51f-001a4a160176 20082946 Isotretinoin (13-cis-retinoic acid), a vitamin A derivative, activates nuclear (retinoid) receptors and regulates transcription. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D000077146 Phenotype 6e2acd84-bc35-11e5-8d2d-001a4ae51247 PMC4331512 Efficient glucuronide hydrolysis by adenoviral expression of beta-glucuronidase We previously showed that intratumoral injection of Ad/mβG, which allows expression of murine beta-glucuronidase as a membrane-anchored form on the surface of infected cells, can enhance the anti-tumor activity of CPT-11 [47]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0045444 Phenotype e6f9cd5c-a5c5-11e7-8112-001a4a160175 PMC5617156 After transfection,cebpβgene and protein expression remained unchanged in treated cells (Fig 2), demonstrating that the polyphenol, and reportedly its glucuronide metabolites, inhibit the process of adipogenesis, at least in part, via miR-155. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006695 Phenotype a17186b3-f53e-11eb-adc4-001a4a160175 29305228 Resveratrol glucuronide can reduce cholesterol synthesis in liver, through mechanism only in part elucidated. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases MESH:D001622 Phenotype c853a036-bc41-11e5-9b9d-001a4ae51247 10.1016/j.ijpara.2009.11.003 As the co-infection progressed to week 5 p.i., additional variations in metabolite composition were noted; decreased levels of betaine and TMAO with increased levels of 4-cresol glucuronide and PAG were observed in urine from infected hamsters. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein MESH:D001599 Phenotype dcea75d6-3405-11e8-bf76-001a4a160175 28279930 Therefore,M37andM42were tentatively determined as glucuronide conjugate of hydroxylated and demethylated berberine. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D000069438 Phenotype 434ed02a-c468-11e5-85e4-001a4ae51246 23538201 "A recent study has demonstrated that serum levels of ezetimibe glucuronide increase after either oral or intravenous administration of ezetimibe in rats fed a methionine- and choline-deficient diet (Hardwick et al., 2012)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D001749 Phenotype d408c75c-38ff-11e8-9fbf-001a4a160176 26254697 Interestingly, bladder tumor incidence following prolonged BBN treatment was significantly reduced by the administration of the synthetic retinoid 13-cis-retinoic acid following the cessation of carcinogen treatment, suggesting therapeutic potential for selected retinoids[18]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D063646 Phenotype 9c8075e6-c9fd-11e5-be63-001a4ae51246 14871993 "In clinical trials, 13-cis-retinoic acid has been shown to suppress or reverse epithelial carcinogenesis and to prevent second primary tumors in patients with SCC(4, 5)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009362 Phenotype 60505a04-2144-11e9-91f4-001a4a160176 PMC6359708 For example, urolithin or its glucuronide conjugate, an ellagitannin catabolized by intestinal bacteria, has been reported to increase muscle function in rodents [27], inhibit metastasis of cancer cell lines [28], and protect the impairment of cardiomyocytes [29]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D011355 Phenotype 2bf32356-3917-11e8-8f56-001a4a160175 24480360 The reduced toxicity is mainly due to the hydrophilicity imparted by the glucuronide moiety that prevents passive cellular uptake and further intracellular prodrug activation by lysosomal β-glucuronidase within non-malignant cells. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D011355 Phenotype 7474a69e-bc51-11e5-ac4e-001a4ae51246 PMC179761 "coli- or human β-glucuronidase were equally sensitized to both the glucuronide prodrug DOX-GA3 and the effector doxorubicin produced from it (Figure 12), suggesting good uptake and conversion of the prodrug, but the bacterial enzyme was more efficient." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D011355 Phenotype 0692eb3b-f574-11eb-8dd9-001a4a160176 32668379 Design and synthesis of water-soluble glucuronide derivatives of camptothecin for cancer prodrug monotherapy and antibody-directed enzyme prodrug therapy (ADEPT). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D009538 Phenotype 41a0eb32-c481-11e5-a92e-001a4ae51246 PMC3356293 "In a crossover study of people smoking menthol versus nonmenthol cigarettes, menthol smoking was shown to inhibit the metabolism of nicotine, both by oxidative and by glucuronide conjugation pathways (Benowitz, Herrera, & Jacob, 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0048144 Phenotype b6e31f0c-30fb-11e9-9b28-001a4a160176 PMC6340230 Etretinate, but not 13-cis-retinoic acid, was reported to inhibit DNA synthesis (by 45%), and therefore, inhibited fibroblast proliferation; the researchers concluded that 13-cis-retinoic acid was the more valuable compound for the treatment of fibrotic disorders. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D005047 Phenotype 52010550-c718-11ee-b346-0050569a791b 10.1016/j.lfs.2023.122119 Etoposide and some of its derivates are also inactivated by glutathione and glucuronide conjugations mediated by glutathione S-transferase (GST) and UGT1 enzymes, respectively [72]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0033344 Phenotype 89548b18-c7c6-11ee-9133-0050569a1f61 10.1016/j.fbio.2023.102866 RSV and Glucuronide resveratrol (GRSV) its main metabolite can reduce hepatic cholesterol increasing the synthesis and efflux of bile acids and decreasing the synthesis and increasing cholesterol efflux. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D013261 Phenotype 9278ddaa-c8df-11e5-a1fd-001a4ae51246 16772539 "In conclusion, Mrp2 deficiency in rats is associated with a decreased sterol-lowering effect of ezetimibe that is most likely caused by a reduced intestinal clearance of the glucuronide and a decreased enterosystemic recycling of the parent drug ezetimibe to the intestinal NPC1L1 sterol-uptake transporter compartment." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein MESH:D000077610 Phenotype 13765aa4-cb29-11e5-8189-001a4ae51246 11408365 "A species difference in biliary metabolite profile existed in that bexarotene acyl glucuronide was the predominant metabolite in rat, while in dog the major metabolite was hydroxylated bexarotene acyl glucuronide." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D007972 Phenotype 1e3e0668-3534-11e8-b868-001a4a160176 21726822 13-cis-retinoic acid has been shown to reverse oral leukoplakia, a common premalignant lesion in the mouth.7Low dose maintenance therapy has also been shown to significantly lower the rate of progression of oral leukoplakia. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D007972 Phenotype 0ee800e0-c8eb-11e5-aac1-001a4ae51247 18172244 "Either the toxicities have been too great for general usage despite a definitive positive clinical trial (e.g., 13-cis-retinoic acid for suppressing oral leukoplakia or preventing secondary head and neck cancers) or the compounds have been inactive when subjected to a randomized trial, even in cases in which the phase II studies were promising." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0007155 Phenotype 677020fc-ab5e-11e6-9646-001a4ae51246 PMC5021119 This interaction would lead to the inhibition of phorbol ester‐induced phosphorylation of ERK and downstream suppression of the activation of AP‐1 and NF‐κB. Hesperetin‐3ʹ‐O‐sulfate, hesperetin‐3ʹ‐O‐glucuronide and naringenin‐4ʹ‐O‐glucuronide (2 μM) significantly attenuated monocyte adhesion to TNFα‐activated human umbilical vein endothelial cells (HUVECs)42. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0007155 Phenotype e6f7de20-a5c5-11e7-b7ac-001a4a160176 28946708 UA glucuronide (at 15 μM), but not UA, UB or UB glucuronide, inhibited monocyte adhesion to TNFα-stimulated human aortic endothelial cells (HAECs); a dosage-dependent inhibition of TNFα-induced migration of endothelial cells was also shown for the above-mentioned urolithins [98]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0007155 Phenotype cce066e4-bbf5-11e5-9b9d-001a4ae51247 PMC3679724 Urolithin A glucuronide moderately but significantly inhibited monocyte adhesion to the endothelial cells as well as the migration capacity of these endothelial aortic cells [45]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D000255 Phenotype 271e3536-cb8d-11e5-8106-001a4ae51247 10997931 "In addition, the ATP-dependent uptake of DNP-SG, a typical substrate for cMOAT/MRP2, by canalicular membrane vesicles was inhibited by BIBR 277 and its glucuronide in a concentration-dependent manner withKivalues of 3.44 ± 0.37 and 1.81 ± 0.30 μM, respectively, suggesting that both BIBR 277 and BIBR 277 glucuronide have an affinity for cMOAT/MRP2." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008152 Phenotype 10539d2e-bc1e-11e5-8abe-001a4ae51246 10.1016/j.jchromb.2009.02.057 Interestingly, our method enables the simultaneous determination of raltegravir–glucuronide, giving some insight into the role of the UGT1A1-mediated metabolism of raltegravir. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008152 Phenotype 1bd09826-c743-11ee-ae05-0050569a1f61 10.1016/j.jpha.2023.06.014 At present, it is known that 7-carboxy-cannabidiol (7-COOH-CBD) and its derivates are main metabolites formed in the phase I hepatic metabolism of CBD, and that CBD glucuronide is a major product of its phase II metabolism [62]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008152 Phenotype 848fbaf6-ca01-11e5-b88f-001a4ae51247 16299161 "Accordingly, gemfibrozil was incubated with human liver microsomes in the presence of UDP-glucuronic acid (to support the formation of gemfibrozil glucuronide) and then in the presence of NADPH (to support the metabolism-dependent inactivation of CYP2C8 by gemfibrozil glucuronide)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008152 Phenotype 78098238-c9fe-11e5-be63-001a4ae51246 15102944 "Glucuronide and sulfate products of EE metabolism formed in microsomal and cytosolic subcellular fractions from liver and intestinal incubates were analyzed on a Zorbax RX-C8 (4.6 × 250 mm; Agilent Technologies) analytical column for in vitro incubations, with UV detection at 210 nm and on-line radioactivity detection." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008152 Phenotype 848fbaf6-ca01-11e5-b88f-001a4ae51247 16299161 "The conversion of gemfibrozil to its acyl glucuronide, and the subsequent metabolism-dependent inhibition of CYP2C8 by gemfibrozil glucuronide, could also be demonstrated in vitro by incubating gemfibrozil with alamethicin-activated human liver microsomes and UDP-glucuronic acid (to form the acyl glucuronide), followed by incubation with NADPH." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008152 Phenotype d686b08c-c8ec-11e5-9faa-001a4ae51247 18322071 His results showed that thep-HO-DPH and its glucuronide were the main products of metabolism. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0008152 Phenotype fb2b097a-bbdf-11e5-9b9d-001a4ae51247 PMC4452429 Furthermore, studies in humans demonstrated that the use of 13-cis-retinoic acid (as treatment to nodular acne) decreased metabolism in orbitofrontal cortex, a region associated with depression [119]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002351 Phenotype 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 Ibuprofen-acyl glucuronide also selectively attenuated the TRPA1-dependent component of the proalgesic responses evokedin vivoby formalin or carrageenan, thus underlying the hypothesis that TRPA1 targeting by ibuprofen-acyl glucuronide contributes to both analgesic and anti-inflammatory effects of ibuprofen. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D008727 Phenotype 916acba6-67e0-11e8-8367-001a4a160176 PMC9326878 More recently, rhein acyl glucuronide, the major metabolite of rhein, was found to significantly inhibit methotrexate uptake (in vitro) mediated by human OAT1 (67% inhibition) and OAT3 (89% inhibition)[111]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D008727 Phenotype acf02b3a-c8e8-11e5-9ad8-001a4ae51247 17656469 "Recently, Luo et al. (2007) have reported that DPC 333 may be a substrate for P-glycoprotein and that glucuronide conjugates of DPC 333 may inhibit the Mrp-2-mediated transport of methotrexate." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D004642 Phenotype 222b49fa-3900-11e8-87fd-001a4a160176 26201645 The results indicated that piperine increased theCmaxand AUC of emodin as well as decreasing the AUC andCmaxof emodin glucuronide, which is evidence that piperine may reduce glucuronidation of emodin and enhance its bioavailability. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0007050 Phenotype d59903ec-bc20-11e5-8abe-001a4ae51246 10.1016/j.jff.2010.04.007 However, glucuronide forms of these phytochemicals have also been shown to induce cell cycle arrest. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype e26b4b88-3406-11e8-bf76-001a4a160175 PMC5540807 One of the most frequently used differentiation therapies is the drug-induced differentiation of GSCs by all-trans retinoic acid (ATRA, derivate of vitamin A; ref.20), and by 13-cis-retinoic acid, both of which can achieve high levels in the brain and have been shown to successfully differentiate both neural stem/precursor cells (NSC) and GSCs. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype a1530340-3526-11e8-b868-001a4a160176 23122274 Furthermore, direct determination of glucuronide metabolites may enable the differentiation between recent and chronic drug use. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype e2c845f0-3757-11e8-bf76-001a4a160175 27530131 The differentiation inducer 13-cis-retinoic acid (13-cis-RA) achieved complete responses in a high-risk neuroblastoma phase I study of high-dose (2 weeks on, 2 weeks off) after myeloablative therapy (1), and a randomized phase III study demonstrated that maintenance therapy of high-risk neuroblastoma with 13-cis-RA after completion of cytotoxic consolidation therapy significantly enhanced event-free survival (EFS; ref.2). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype e9a2732a-dcb6-11ea-8ea3-001a4a160176 PMC5920563 Indeed, 13-cis-retinoic acid has been incorporated into frontline therapy for children with high-risk neuroblastoma to induce differentiation in states of minimal residual disease following intensive, multimodality therapy (Shimada et al.1999b). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype 6fc14b14-393d-11e8-87fd-001a4a160176 18639684 Levels of either ATRA or 13-cis-retinoic acid (13-cis-RA) more than 5μmol/L can cause arrest of cell growth and morphological differentiation[4]such as neuritogenesis of human NB cell lines[34]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0030154 Phenotype 80fa6e02-351d-11e8-9192-001a4a160175 PMC5837682 "For instance, a recent study showed that BPA glucuronide can induce lipid accumulation and differentiation of pre-adipocytes (Boucheret al., 2015)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0071897 Phenotype b6e31f0c-30fb-11e9-9b28-001a4a160176 PMC6340230 Etretinate, but not 13-cis-retinoic acid, was reported to inhibit DNA synthesis (by 45%), and therefore, inhibited fibroblast proliferation; the researchers concluded that 13-cis-retinoic acid was the more valuable compound for the treatment of fibrotic disorders. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D051379 Phenotype d93e8358-c957-11ee-b346-0050569a791b 10.1016/j.jchromb.2022.123567 With GLXB herb pair intervention, the level of indoxyl glucuronide was restored, indicating the possible role of GLXB herb pair in the regulation of pentose and glucuronate interconversions pathway in 9-week mice with AS. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D051379 Phenotype 5b2f087a-ca00-11e5-b88f-001a4ae51247 PMC511036 Interestingly, isotretinoin (13-cis-retinoic acid) reduces A2E deposition in RPE cells ofAbcr–/–mice by a similar magnitude (26). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D051379 Phenotype f29fad6c-c470-11e5-a92e-001a4ae51246 19889793 It was also reported that the plasma concentration of resveratrol glucuronide was markedly decreased inMrp3(−/−) mice after oral administration of resveratrol. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006915 Phenotype 677020fc-ab5e-11e6-9646-001a4ae51246 PMC5021119 In HUVECs, apoptosis induced by high glucose was inhibited dose‐dependently by quercetin sulfate/glucuronide (300 nM), in addition to H2O2quenching, inhibition of JNK and of caspase‐3 activity82. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006915 Phenotype 5f78affc-bc3c-11e5-ac4e-001a4ae51246 PMC3972687 Notably, 13-cis-retinoic acid, a drug commonly used for high-risk NB, can reduce apoptosis mediated by several chemotherapeutics through upregulating Bcl-2 and Bcl-XL, when applied in combination with those agents in several NB cell lines [169]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0006915 Phenotype 4adef44a-391a-11e8-87fd-001a4a160176 21856292 Moreover, considering the limited oral bioavailability of quercetin and its rapid metabolism in cells, the report that itsO-methylated and glucuronide metabolites were able to inhibit the AKT/PKB and ERK1/2 pathways and, thus, induce apoptosis[63]was particularly interesting. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008219 Phenotype 60f69c52-c9fe-11e5-b88f-001a4ae51247 15520197 In 1985, Helson and Helson(9)reported that the cell line SK-N-DZ was the only line in which 13-cis-retinoic acid caused cell death. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008219 Phenotype 33bb6422-bc37-11e5-9b9d-001a4ae51247 PMC2935367 In fact, reducing GSH levels through buthionine sulfoximine treatment, resulted in increased sensitivity of HTLV1 transformed cells to 13-cis-retinoic acid induced cell death[71]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0008219 Phenotype fb2b097a-bbdf-11e5-9b9d-001a4ae51247 PMC4452429 The mechanism by which 13-cis-retinoic acid altered neurogenesis and induced cell death in mice hippocampus is not clear, but it has been reported that this retinoid may trigger apoptosis through activation of caspase-3 and by modulating bcl2 and p53 gene expression in melanoma cells [135]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0006954 Phenotype f8bd9a48-bbf0-11e5-9b9d-001a4ae51247 10.1016/j.bmcl.2011.07.086 Some flavonoid glycosides have been reported to be deconjugated into aglycone by β-glucuronidase released from neutrophils after the induction of inflammation.32,33Urolithin A glucuronide in plasma may also serve to reduce the inflammation after deconjugation at the inflamed site. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0001649 Phenotype 0566eaaa-bbd9-11e5-8abe-001a4ae51246 10.1016/j.nutres.2012.09.018 Another study by the same group demonstrated that hesperetin-7-O-glucuronide, a form of conjugated glucuronide hesperidin, stimulated osteoblast differentiation by up-regulating mRNA gene expression (eg, ALP, Runx2, and osterix) and induced phosphorylation of Smad1/5/8 in primary rat osteoblasts[59]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D015248 Phenotype dbde4c98-3758-11e8-8f56-001a4a160175 27457785 However, the mechanism of gemfibrozil-mediated DDI and clinical DDI data with cerivastatin have already found that gemfibrozil increased the plasma concentration of cerivastatin with the inhibition of CYP2C8 and OATP1B1 by gemfibrozil glucuronide (Backman et al., 2002;Shitara et al., 2004;Kudo et al., 2013). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D015951 Phenotype 9c8a9938-bc4a-11e5-ac4e-001a4ae51246 10.1016/j.ejphar.2011.10.009 Inhibition of factor Xa activity in human plasma Darexaban and darexaban glucuronide inhibited factor Xa activity in human plasma in a concentration-dependent manner with EC50values of 3.4μM (95% CI: 3.1–3.7) and 1.1μM (1.0–1.2), respectively (Fig. 3). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0035148 Phenotype e0ab6674-bc54-11e5-9b9d-001a4ae51247 PMC3952051 Moreover, 13-cis-retinoic acid was able to inhibit vascular endothelial cell proliferation, migration and tube formation. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0101023 Phenotype e0ab6674-bc54-11e5-9b9d-001a4ae51247 PMC3952051 Moreover, 13-cis-retinoic acid was able to inhibit vascular endothelial cell proliferation, migration and tube formation. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002277 Phenotype e3d80532-d4c3-11e5-b878-001a4ae51246 719631 At the two dose levels of OH-BBN, feeding of 13-cis-retinoic acid reduced the incidence of both carcinomas and noninvasive papillomas, as well as the extent of neoplastic development in the urinary bladder. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002277 Phenotype 3d688334-cb2c-11e5-9aa0-001a4ae51247 12124333 "Treatment with 13-cis-retinoic acid has been demonstrated to reduce the occurrence of second primary carcinomas in patients with previously resected head and neck carcinomas(9)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D003474 Phenotype d2e221d4-ea3d-11ee-b22c-0050569a1f61 10.1016/j.jnutbio.2022.109083 However, an increase in blood curcumin glucuronide concentration enhances the concentration of free-form curcumin, resulting in the suppression of human colon carcinomas implanted in mice[44]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D003474 Phenotype 2e7d66ca-c79d-11ee-b346-0050569a791b 10.1016/j.foodres.2023.113070 Compared to free substances and physical mixing systems, the kneading-fabricated curcumin-piperine-hydroxypropyl-β-cyclodextrin delivery system effectively promoted nutrient permeability through the simulated gastrointestinal tract wall and blood–brain barrier, and piperine is a known glucuronide inhibitor that blocks the metabolic inactivation of curcumin (Stasilowicz et al., 2020). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D013481 Phenotype 34ee5c4c-bc40-11e5-8d2d-001a4ae51247 10.1016/j.freeradbiomed.2011.06.002 The observation that specific metabolites of (−)-epicatechin (3′- and 4′-O-methyl-(−)-epicatechin and (−)-epicatechin glucuronide) can inhibit NADPH-oxidase and consequently diminish superoxide anion production and NO bioavailability[53,54]strongly supports an alternative mechanism for the effects of flavanols on NO-dependent cell signaling and, as a result, on vascular function, inflammation, and hypertension. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D014970 Phenotype a5acb850-c8e5-11e5-9624-001a4ae51246 17478601 "Glucuronide conjugation at the 3- and 7-positions reduces dramatically the inhibition of xanthine oxidase and lipoxygenase (Day et al., 2000), whereas glucuronide conjugation at the 3′- and 4′-positions reduces the ability to prolong the lag time of human low-density lipoprotein oxidation in vitro (Janisch et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0016049 Phenotype 6fc14b14-393d-11e8-87fd-001a4a160176 18639684 Levels of either ATRA or 13-cis-retinoic acid (13-cis-RA) more than 5μmol/L can cause arrest of cell growth and morphological differentiation[4]such as neuritogenesis of human NB cell lines[34]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0016049 Phenotype 2d435882-bc16-11e5-9b9d-001a4ae51247 PMC4401015 Sulfate and glucuronide metabolites were reported to inhibit colon cancer cell growth [22,27,28]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D003967 Phenotype 30849c92-ea1e-11ee-b346-0050569a791b 10.1016/j.bcp.2022.115209 For example, diarrhea is caused by the excretion of SN-38 glucuronide into the intestinal lumen, which regenerates SN-38 in the presence of intestinal bacteria and is locally toxic to the intestinal epithelium[241]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D003967 Phenotype b6cd14bc-791e-11ee-add2-0050569a791b 10.1007/s12029-022-00840-0 Diarrhea is related to concentrations of SN-38 at the intestinal lumen resulting from the biliary excretion of SN-38 and potentially enhanced by the intraluminal conversion of SN-38 glucuronide (SN-38G) to SN-38 by bacterial glucuronidases [4]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D006220 Phenotype 44c4aa92-c47c-11e5-9cc6-001a4ae51246 22028316 "In plasma, the concentration of haloperidol glucuronide is highest among the metabolites, followed, in rank order, by unchanged haloperidol, reduced haloperidol, and reduced haloperidol glucuronide (Someya et al., 1992)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D006220 Phenotype 44c4aa92-c47c-11e5-9cc6-001a4ae51246 22028316 "In plasma, the concentration of haloperidol glucuronide is highest among the metabolites, followed, in rank order, by unchanged haloperidol, reduced haloperidol, and reduced haloperidol glucuronide (Someya et al., 1992)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0045730 Phenotype 3fc494fc-bc0d-11e5-8abe-001a4ae51246 PMC4548092 In addition, ERK-phosphorylation, release of glucuronide and C5a induced oxidative burst (superoxide anion production) were also inhibited by resveratrol. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009447 Phenotype 959dbbb0-ac41-11ee-a19b-0050569a791b PMC7434894 Retinoids are vitamin A analogues that induce tumour cell differentiation,63and 13-cis-retinoic acid treatment of neuroblastoma cells in vitro both induces neuroblastoma cell differentiation and reduces neuroblastoma cell proliferation.64,65–6613-cis-retinoic acid is also currently a component of standard maintenance therapy in the most common protocols utilised for the treatment of children with high-risk neuroblastoma.35Morphologic neuroblastoma cell differentiation induced by retinoids in vitro occurs over the course of 7–10 days, but the pathways activated prior to the morphologic differentiation are poorly understood. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D009447 Phenotype 0795bc6c-bc00-11e5-8abe-001a4ae51246 10.1016/S0006-291X(03)00177-3 A recent clinical trial showed that 13-cis-retinoic acid (13RA), used as a chemo-preventive agent after conventional chemo-radiotherapy, increased the survival rates of patients with advanced stage neuroblastoma[12]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates GO:0000746 Phenotype 50365576-c944-11ee-9133-0050569a1f61 10.1016/j.jnutbio.2022.109219 Synthesis and purification of lignan glucuronides ED glucuronide (EDGlu) was synthesized using a polyphenol conjugation protocol [28,29]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0000746 Phenotype b2f2fdba-bc03-11e5-8abe-001a4ae51246 10.1016/S0278-6915(00)00110-1 We propose that retinol may be causing potentiation through a mechanism of glucuronide saturation, which would limit the capacity of this major conjugation pathway, and are currently investigating this aspect. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D007052 Phenotype ff416e2e-c485-11e5-a92e-001a4ae51246 23052971 "For ibuprofen, most attention has focused on the chemical reactivity of its acyl glucuronide metabolite, where reports demonstrated it to mediate the covalent binding of ibuprofen to plasma protein and human serum albumin in vitro (Castillo and Smith, 1995;Castillo et al., 1995)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0051923 Phenotype 19ff1de2-c472-11e5-91a7-001a4ae51247 19995888 "This finding is in agreement with many well known examples of carboxylate-containing compounds that exhibit high levels of biliary elimination such as irinotecan (carboxylate form), methotrexate, bile acids (such as taurocholic acid), and glucuronide, glutathione, and sulfation conjugates derived from the parent compounds." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D006540 Phenotype 65c42316-bbf4-11e5-9b9d-001a4ae51247 10.1016/S1095-6433(00)00293-2 Although nonylphenol diethoxylate and prochloraz were not metabolized by gill pavement cells in primary culture, traces of glucuronide conjugate of 2,4-dichloroaniline (degradation product of some herbicide and intermediate in the production of dye) were observed in culture medium (Cravedi and Leguen, unpublished results). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D015262 Phenotype 7785db2c-f577-11eb-8edb-001a4a160176 32301032 Theβ-glucuronidase, produced by intestinal bacteria, hydrolyzes glucuronide, liberate xenobiotics and eventually results in the toxicity in the intestine and decreases the rate of excretion of xenobiotic through reabsorption [15]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D013656 Phenotype 3d12c1bb-e1e6-11e9-a35a-001a4a160175 PMC6760779 Progesterone, ursodeoxycholic acid, and lesinurad were also inhibitors with IC < 20 μM. Finally, the three steroid glucuronide conjugates, androsterone glucuronide, etiocholanolone glucuronide, and androstanediol-3-glucuronide, achieved IC values for inhibition of SLC22A24-mediated taurocholic acid uptake of 45 ± 29 μM, 57 ± 36 μM and 21 ± 11 μM, respectively (Table 3). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D004202 Phenotype 005133a8-352c-11e8-a34b-001a4a160175 27341547 We report on a false-positive EtG immunoassay result caused by excessive urinary isopropyl glucuronide excretion most probably due to hand or surface disinfectant abuse. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D002295 Phenotype e3d80532-d4c3-11e5-b878-001a4ae51246 719631 In mice receiving the lower dose of OH-BBN, the feeding of 13-cis-retinoic acid prevented the appearance of both squamous and transitional cell carcinomas with a reduction in incidence from 33 to 0% (p less than 0.01). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits GO:0070731 Phenotype a9c48625-f53a-11eb-ac6f-001a4a160175 29627501 Due to the structural similarity of ZEN and 17β-estrodiol, the ZEN glucuronide conjugate may also inhibit the cGMP transport which could induce the downregulation of ABCc5. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D005227 Phenotype 4efee8a8-3534-11e8-9192-001a4a160175 21798251 Cell pre-treatment with the glucuronide metabolites significantly inhibited the formation of MDA and fatty acid and cholesterol major oxidation products, HP and 7-keto. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D012008 Phenotype 5b9f1bd6-c471-11e5-85e4-001a4ae51246 19138978 "In patients with a history of SCCHN, chemoprevention with high-dose 13-cis-retinoic acid reduced the recurrence rate of OPLs and decreased the risk of second primary tumors (14)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D012008 Phenotype 9ddc6ce0-bc44-11e5-8d2d-001a4ae51247 10.1016/j.semcancer.2011.08.001 The authors concluded that 13-cis-retinoic acid could be beneficial for patients with minimal residual disease as maintenance therapy to prevent or delay recurrence with limited toxicity. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D012008 Phenotype 3e5ce8b2-c473-11e5-91a7-001a4ae51247 PMC2964280 "Materials and Methods Study population and epidemiologic data The subjects included in this study were participants enrolled (1991-1999) in the Retinoid Head and Neck Second Primary Trial designed to evaluate whether daily low-dose 13-cis-retinoic acid (13-cRA) prevents SPT or tumor recurrence in early-stage HNSCC patients (1)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D012008 Phenotype 5fea705c-c998-11ee-b346-0050569a791b 10.1016/j.yexcr.2022.113412 To apply the depletion of BMI1 to the development of molecular-targeted therapy, we investigated the effects of the combination of ATRA and BMI1 KD in NB cellsin vitroandin vivobecause treatment with the retinoid, 13-cis-retinoic acid (isotretinoin) was previously shown to reduce the risk of recurrence after high-dose chemotherapy and stem cell transplant [25]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D001284 Phenotype a6cc1eae-72d0-11ee-9572-0050569a1f61 10.1007/s11418-023-01726-6 Naringenin and naringenin glucuronide metabolized from 1 reversed Aβ-induced axonal atrophy and were detected in brain and plasma of 5XFAD mice [10], and 2 showed a better activity than 1 on osteogenic differentiation in MC3T3-E1 cells [4]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D010212 Phenotype f16941c2-bbdf-11e5-8abe-001a4ae51246 PMC3984781 This study showed that both retinyl palmitate and 13-cis-retinoic acid inhibited the development of skin papillomas and also had a marked effect on skin cancers [31]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D010212 Phenotype e3d80532-d4c3-11e5-b878-001a4ae51246 719631 At the two dose levels of OH-BBN, feeding of 13-cis-retinoic acid reduced the incidence of both carcinomas and noninvasive papillomas, as well as the extent of neoplastic development in the urinary bladder. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D000082 Phenotype 92deedc6-c75e-11ee-b346-0050569a791b 10.1016/j.bioorg.2023.106722 The sulphate and glucuronide cofactors (PAPS and UDPGA), on the other hand, become depleted when large amounts are taken, which causes more paracetamol to be metabolized to the reactive intermediate. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D000082 Phenotype ca67cdd6-374e-11e8-a51f-001a4a160176 28919358 The quantity of glucuronide, cysteine,N-acetyl cysteine and glutathione metabolites was increased by elevating acetaminophen concentration from 1mM to 13mM. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D018365 Phenotype 23596516-c47f-11e5-85e4-001a4ae51246 PMC2955783 Children with high-risk neuroblastoma are generally treated with intensive multi-modal chemotherapy, with 13-cis-retinoic acid included in the final part of the treatment regimen in an effort to eliminate minimal residual disease (11,12). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D047310 Phenotype 8997e87c-3509-11e9-8741-001a4a160176 PMC6225362 Thus, M7 was identified as sulfate and glucuronide conjugation product of apigenin. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits MESH:D008139 Phenotype 615e81cc-c47d-11e5-85e4-001a4ae51246 PMC2895033 Drug-drug interactions would not be expected with loperamide and flavopiridol, which is eliminated primarily by glucuronidation and biliary excretion of both parent and glucuronide metabolites.38–41Additionally, our flavo-G data do not support the latter hypothesis, as we saw no indication of upregulation of UGT activity between days 1 and 3 (data not shown). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates MESH:D001930 Phenotype c4675566-3517-11e8-9fbf-001a4a160176 22316499 Given that both glucuronide metabolites are found in the plasma (Mazoit et al., 2007), basally and elevated following brain injury in the CSF (Morgan et al., 2008), at concentrations equal to or exceeding morphine, it is likely that these metabolites are important contributors to glial activation and associated downstream proinflammatory events induced following morphine administration. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases PF:PF01752 ProteinFamily b1549ec4-bbd5-11e5-956b-001a4ae51247 PMC4616673 Thus, the increased level of dopamine glucuronide observed in our study may be a potential biomarker involved in the onset of CKD-MBD.13It has been reported that serotonin increases the PTH effect on activating protein-1 activity, particularly on the regulation of collagenase expression.14The increasedN-acetylserotonin glucuronide in high-PTH patients may indicate that serotonin may be involved in the development of CKD-MBD. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates PF:PF08765 ProteinFamily f303bf26-3388-11e8-b868-001a4a160176 21396918 The former metabolite has been classified as a weak MOR ligand, while the latter glucuronide is a strong activator of MOR-induced signaling with potencies comparable to morphine. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates PF:PF12252 ProteinFamily bc2d12aa-3512-11e8-8636-001a4a160175 26874932 Side effects of MMF are induced by another metabolite – an acyl glucuronide form (Ac-MPAG) – through the stimulation of cytokine secretion by mononuclear leukocytes[73]. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits PF:PF07897 ProteinFamily cef9691e-3405-11e8-a34b-001a4a160175 28259683 Hamster ear sebaceous glands were reduced in size by approximately 50% with topical 13-cis-retinoic acid treatment. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates FPLX:TXNRD ProteinFamily df4afc2a-c467-11e5-a92e-001a4ae51246 PMC3652062 Nevertheless, we previously reported (25) that auranofin and 13-cis-retinoic acid at the concentrations used in the present study predominantly inhibit thioredoxin reductase and not glutathione reductase, suggesting that the glutaredoxin system is not likely involved in LTCC adrenergic control in this rat model. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 increases FPLX:LDH ProteinFamily 6ca16f96-ae95-11ec-b4ed-0050569a1f61 PMCPMC8228354 p-Cresol sulfate reduced total cellular GSH concentration (by 30.5 ± 13.6%,p< 0.05,Figure 7b), whereas bothp-cresol sulfate andp-cresol glucuronide slightly increased LDH release compared to the vehicle control (Figure 7c). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:NADPH:oxidase ProteinFamily 956d7d9c-bc03-11e5-9b9d-001a4ae51247 10.1016/j.fct.2013.02.020 PB2 dimer and to a lesser extent EC and related metabolites [3′-O-methyl epicatechin, 4′-O-methyl epicatechin, and (−)-epicatechin glucuronide] inhibited the activity of NADPH-oxidase in cultures of human umbilical vein endothelial cells (Steffen et al., 2008, 2007). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:NADPH:oxidase ProteinFamily 34ee5c4c-bc40-11e5-8d2d-001a4ae51247 10.1016/j.freeradbiomed.2011.06.002 The observation that specific metabolites of (−)-epicatechin (3′- and 4′-O-methyl-(−)-epicatechin and (−)-epicatechin glucuronide) can inhibit NADPH-oxidase and consequently diminish superoxide anion production and NO bioavailability[53,54]strongly supports an alternative mechanism for the effects of flavanols on NO-dependent cell signaling and, as a result, on vascular function, inflammation, and hypertension. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:CYP ProteinFamily 2bd06e3c-ae94-11ec-a61d-0050569a1f61 PMCPMC8552062 Metabolites-mediated DDI attributed to the inhibition of cytochrome P450 enzymes by glucuronide metabolites are relatively common in clinical scenarios (Isoherranen et al., 2009). 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:CYP ProteinFamily 9b29aeb0-c471-11e5-91a7-001a4ae51247 19773535 "In addition to inhibiting CYP2C8, gemfibrozil and/or its glucuronide can competitively inhibit some other P450 enzymes and organic anion-transporting polypeptide (OATP) 1B1 in vitro (Wen et al., 2001;Shitara et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:ERK ProteinFamily 4adef44a-391a-11e8-87fd-001a4a160176 21856292 Moreover, considering the limited oral bioavailability of quercetin and its rapid metabolism in cells, the report that itsO-methylated and glucuronide metabolites were able to inhibit the AKT/PKB and ERK1/2 pathways and, thus, induce apoptosis[63]was particularly interesting. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits PF:PF09213 ProteinFamily c1085f38-89ac-11ee-9572-0050569a1f61 10.1007/s00204-022-03289-z M3 and M4 fragmentation yielded ACZ major fragments m/z 220.9808 and 222.9954 in HESI(−) and HESI(+), respectively, produced by glucuronide loss. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 hydroxylatesProtein PF:PF09213 ProteinFamily 113f3ace-c482-11e5-9cc6-001a4ae51246 22930276 "The major metabolites of AMG 853 in vitro include an acyl glucuronide metabolite (M1), at-butyl-hydroxylated metabolite (M2), and a chlorocyclopropylphenyl-hydroxylated metabolite (M3)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits FPLX:Cyclin ProteinFamily a63293d4-c9fe-11e5-be63-001a4ae51246 15073138 Perhaps 13-cis-retinoic acid activated cyclin degradation in these cases. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 inhibits IP:IPR000907 ProteinFamily a5acb850-c8e5-11e5-9624-001a4ae51246 17478601 "Glucuronide conjugation at the 3- and 7-positions reduces dramatically the inhibition of xanthine oxidase and lipoxygenase (Day et al., 2000), whereas glucuronide conjugation at the 3′- and 4′-positions reduces the ability to prolong the lag time of human low-density lipoprotein oxidation in vitro (Janisch et al., 2004)." 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 decreases FPLX:FABP ProteinFamily e760bb88-bc39-11e5-8abe-001a4ae51246 PMC3782695 Azorín-Ortuñoet al.[251] described that 100 nM RES or DH-RES, but not their corresponding glucuronide metabolites, decreased fatty acid binding protein type-4 (FABP4) levels in macrophages exposed to oxidized LDL particles. 1 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 activates IP:IPR013172 ProteinFamily 13007d44-ae93-11ec-840e-0050569a791b PMCPMC8599868 In addition, p-tolyl glucuronide increased from 21 to 180 DIM for NAH cows reaching greater concentrations than their NZH counterparts (Fig. 2c). 1 CHEBI:29101 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 5167df08-cb2a-11e5-a6cd-001a4ae51247 PMC129455 "Instead,S. agalactiaehas a galactitol PTS, a ribose ABC transporter, a gluconate transporter, and a sodium ion-driven glucuronide uptake system, correlating with the novel pathways present inS." 1 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 39e8bc00-c8e9-11e5-9624-001a4ae51246 18474677 Mrp2 also mediates the mucosal efflux of the glucuronide conjugates of xenobiotics into the lumen (Adachi et al., 2005). 1 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 1731b1b8-ca00-11e5-be63-001a4ae51246 15507541 ATP-dependent transport of [3H]LTC4and [3H]E217βG was readily observed in both vesicles (Fig. 4), confirming that dog Mrp2 accepts glutathione and glucuronide conjugates as substrates. 1 UNIPROT:A8MT33 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein b9e92de0-c484-11e5-91a7-001a4ae51247 PMC3422542 "VPA glucuronide is a substrate of Mrp2 (Khemawoot et al., 2007), and Mrp2 deficiency almost completely eliminates active secretion of the acyl glucuronide metabolite of VPA across the canalicular membrane, with a nearly complete reduction of choleresis associated with movement of VPA glucuronide into bile (Wright and Dickinson, 2004)." 1 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein f3cc085c-c470-11e5-9cc6-001a4ae51246 PMC2812073 "MRP2 mediates the ATP-dependent efflux of glutathione, glucuronide, and sulfate conjugates of endo- and xenobiotics, can mediate the efflux of chemotherapeutic drugs such as methotrexate, and is capable of GSH-stimulated transport of nonconjugated drugs, such as anthracyclines and Vinca alkaloids (Deeley et al., 2006)." 1 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9a650e98-c8e5-11e5-a1fd-001a4ae51246 17470645 "For the efflux transport of glucuronide conjugates in the luminal side, MRP2 and BCRP have been shown to mediate the intestinal efflux of the glucuronide conjugates of xenobiotics (Adachi et al., 2005)." 1 UNIPROT:A8MT33 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 24858d08-bc31-11e5-8d2d-001a4ae51247 PMC3777468 In recent reports, significant accumulation of etoposide glucuronide in the liver inMrp2−/−/Mrp3−/−mice was described, but neither single knockout showed this phenomenon, indicating an alternative pathway provided by Mrp2 and Mrp3 for hepatic elimination of etoposide glucuronide[80]. 1 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 8621095a-c9fd-11e5-b88f-001a4ae51247 14976346 "The multidrug resistance–associated protein 2 (Mrp2), located in the canalicular membrane, mediates the rate-limiting step in the biliary secretion of different organic anions, including glutathione (GSH)-S-conjugates of leukotriene-C4 or bromosulphophthalein (BSP), glucuronide conjugates of bilirubin, estrogens, and bile salts, and both reduced and oxidized GSH (Koniget al., 1999;Paulusmaet al., 1999)." 1 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9278ddaa-c8df-11e5-a1fd-001a4ae51246 16772539 "In this study, the absence of intestinal and hepatic Mrp2 in our TR-negative rats resulted in manyfold increased serum glucuronide concentrations, a significantly increase of urinary excretion at unchanged renal clearance, and a nearly abolished intestinal clearance." 1 UNIPROT:A8MT33 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3ec38db4-ca00-11e5-ab20-001a4ae51246 15466492 "These findings, together with our present results, give rise to the view that in pregnancy, low expression of MRP2 limits the transport rate of the bisphenol A glucuronide into the bile and that sinusoidal transporting systems such as MRP1 and MRP3 compensate by transporting the glucuronide into the vein." 1 UNIPROT:A8MT33 decreases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9278ddaa-c8df-11e5-a1fd-001a4ae51246 16772539 "That means, according to our hypothesis, that the decrease or the absence of intestinal (and hepatic) “first-pass” secretion of the glucuronide caused by Mrp2 deficiency reduces or even interrupts recycling of the active compound ezetimibe to the NPC1L1 receptor compartment." 1 UNIPROT:A8MT33 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3ec38db4-ca00-11e5-ab20-001a4ae51246 15466492 "During and after perfusion of 50 μM bisphenol A to the EHBR liver, the bisphenol A glucuronide was almost all excreted into the vein, indicating that MRP2 mediates bilious excretion of the glucuronide (Fig. 3)." 1 UNIPROT:A8MT33 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 03adc30a-c467-11e5-85e4-001a4ae51246 24346835 "This DDI is consistent with reduced enterohepatic cycling due to inhibition of ezetimibe glucuronide hepatic transport by OATP1B1 and possibly MRP2, as well as inhibition of intestinal efflux of both parent and glucuronide by P-gp and MRP2." 1 UNIPROT:Q92887 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 15def204-bc53-11e5-9b9d-001a4ae51247 PMC4683916 The concurrent use of tacrolimus may decrease the mycophenolic acid concentration, thereby leading to an increased dose of MMF.1718Contradictory results have also been reported, in that co-administration with cyclosporine required significantly higher doses of MMF to achieve similar mycophenolic acid levels as tacrolimus-treated patients.19It has also been suggested that the cyclosporine-mediated inhibition of the biliary excretion of mycophenolic acid glucuronide by the multidrug resistance-associated protein-2 transporter is the mechanism responsible for the interactions between cyclosporine and MMF. 1 UNIPROT:Q92887 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 56776d6a-c472-11e5-9da3-001a4ae51247 19525466 "Here, we report studies that led us to the ABC subfamily C member 2 (Abcc2)—which mediates the secretion of amphiphilic glutathione, glucuronide, and sulfate conjugates into bile (5,10)—as the major relevant bile canalicular transporter of99mTc-mebrofenin." 1 UNIPROT:P48845 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein bc8ed6d9-f53b-11eb-ba73-001a4a160176 29222744 Furthermore, DEX also markedly increased the biliary excretion of IBU (1.7 fold) and its glucuronide (3.3 fold) in IBU-treated rats (Fig.7e). 1 MESH:D000666 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype e302bbd2-d74a-11e5-b317-001a4ae51247 PMC444268 Potentiation of the antifungal effects of antibiotics by amphotericin B.61-5Amphotericin B was found to potentiate the antifungal effects of mycophenolic acid glucuronide, tetracycline, and actinomycin D by increasing the penetration of these antibiotics through the fungal cytoplasmic membrane. 1 UNIPROT:Q9U1H9 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 628953e0-bc2d-11e5-ac4e-001a4ae51246 PMC4295395 Subjects on SBR also had decreased plasma glucuronide and sulfate metabolites and an increase in urinary sulfate metabolite, suggesting an alteration of phase II metabolism. 1 FPLX:MRPS activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily cc8b55e1-f596-11eb-900c-001a4a160175 31029799 As one of the most important drug efflux transporters, the major physiologic function of MRPs is to mediate ATP-dependent transport of glutathione, glucuronide, and sulfate conjugates metabolites into the bile canaliculus in the livers [35]. 1 FPLX:MRPS activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 749cc17c-c9ff-11e5-ab20-001a4ae51246 15205392 Members of the ABC family of MRPs, such as MRP1, MRP2, and MRP3, accept glucuronide conjugates. 1 UNIPROT:O15439 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 85cb2384-ca00-11e5-9b70-001a4ae51247 15284287 "The substrates of MRP2 include glutathione and glucuronide conjugates and certain types of unconjugated amphipathic organic anions as well as PAH (36,39⇓), whereas MRP4 has been shown to accept cyclic nucleotides (37), estradiol 17β glucuronide, and methotrexate." 1 UNIPROT:O15439 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein fa4f7cda-c8e5-11e5-9624-001a4ae51246 17682070 On the contrary, MRP4 accepts only edaravone glucuronide (Figs.1Band3). 1 UNIPROT:O15439 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 0aae6d66-5ca1-11e7-b441-001a4ae51247 26758854 On the contrary, MRP4 knockdown led to a significant elevation (P< 0.05) in intracellular glucuronide (Supplemental Fig. 1B). 1 UNIPROT:P08236 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 6e2acd84-bc35-11e5-8d2d-001a4ae51247 PMC4331512 colias opposed to beta-glucuronidase expressed in cancer cells after administration of Ad/mβG. Release of beta-glucuronidase from bacteria increases hydrolysis of a systemically administered glucuronide probe To investigate if the limited probe hydrolysis by poor contact between beta-glucuronidase inE. 1 UNIPROT:O75795 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a57febc2-c47b-11e5-9cc6-001a4ae51246 21673130 "From the tested UGTs, only UGT1A9, UGT1A4, UGT2B7, UGT2B4, and UGT2B17 produced significant amounts of eslicarbazepine glucuronide." 1 UNIPROT:O75795 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 38b398e6-5c0e-11e7-b83b-001a4ae51246 PMC5464342 Our assay was not designed to identify phase II metabolites suggesting that the two additional peaks observed in the previous study may correspond to conjugated metabolites, such as the 17β‐DHE‐glucuronide produced by UGT2B17 (Sun et al.2010). 1 UNIPROT:P54855 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 99773bd8-c8e9-11e5-a1fd-001a4ae51246 18719240 "The commercial UGT2B15 sample was clearly more active and also produced a trace amount of 3-OH glucuronide of β-estradiol, but 17-O-glucuronides were still not detected." 1 UNIPROT:P54855 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 834dc114-c9fd-11e5-be63-001a4ae51246 14977865 "In the present study, diclofenac (500 μM) was found to be a potent inhibitor of phenolic glucuronide formation by UGT2B15 (88%) as well as by human liver (>89%) and human jejunum microsomes (84%)(Table 5)." 1 MESH:D004953 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 8a3dc720-c70c-11ee-9133-0050569a1f61 10.1016/j.xagr.2023.100266 After oral administration, E4 is rapidly absorbed with high bioavailability (70%) and a long half-life (>24 h),26,27which differs from EE28–30and estradiol (E2) (Table 1).29,31Estetrol metabolism via UDP-glucuronosyltransferases and sulfotransferases lead to inactive glucuronide and sulfate conjugates that are excreted in urine. 1 CHEBI:4806 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1597e8de-c467-11e5-9da3-001a4ae51247 24343359 "EGCG reduces microsomal vessel uptake of glucuronide by 90%, interfering with carcinogen reactivation (12)." 1 CHEBI:4806 methylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 11ffc974-390b-11e8-87fd-001a4a160176 25453543 Epigallocatechin gallate metabolites can exist in methylated, glucuronide (and/or sulfoglucuronide), and sulfated forms. 1 CHEBI:4806 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 707b650c-bc54-11e5-8d2d-001a4ae51247 10.1016/j.biocel.2007.01.010 The assumption that EGCG reduces glucuronidase activity by inhibiting glucuronide entry into the ER was confirmed by direct transport measurements. 1 CHEBI:5633 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 8a74663a-c47d-11e5-a92e-001a4ae51246 20713656 "We also found that the formation rates of 4-hydroxymidazolam glucuronide I were strongly inhibited by hecogenin (10 μM, ∼95%) (Fig. 4)." 1 MESH:D010664 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 05070ab2-c481-11e5-8491-001a4ae51247 PMC3336811 "Cotreatment with phenylmethylsulfonyl fluoride decreased the futile cycling of the parent zomepirac and its glucuronide and increased the plasma clearance of zomepirac." 1 MESH:D009020 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 44da0abc-bbd6-11e5-956b-001a4ae51247 10.1016/j.pneurobio.2011.11.001 Morphine activates the 5-α reductase II (SRD5A2) enzyme and therefore enhances the metabolism of testosterone to DHT and 3alpha-diol glucuronide in rat brains (Amini and Ahmadiani, 2005). 1 MESH:D009020 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 6fd096e8-bbd4-11e5-956b-001a4ae51247 10.1016/j.ajp.2012.12.001 Plasma morphine 6 glucuronide levels increased while plasma morphine levels decreased, implying morphine's conversion to morphine 6 glucuronide. 1 MESH:D013928 decreases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 637b52bc-8dff-11e7-82ff-001a4ae51246 27179126 The CID of M6 produced the main product ion atm/z478.1434, a result of loss of glucuronide and CO2, and other product ions atm/z522.1334 (loss of C6H8O6), 463.1204, and 383.1267. 1 MESH:D013928 methylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype b31bdcfa-c8e5-11e5-9624-001a4ae51246 17496205 "The position of glucuronide was established at the phenolic hydroxyl group from the differences in the CID product ion spectra of methylated products of 4′-hydroxy-TRX, and its glucuronide conjugate." 1 MESH:D000431 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d02f4d74-3551-11e8-a51f-001a4a160176 19237197 A small fraction of the aliphatic alcohols may be eliminated unchanged or as the glucuronide conjugate (Kamil et al., 1953). 1 MESH:D000431 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype a9f16d58-3806-11e6-9aa8-001a4ae51247 25754126 Alcohol consumption is reported to increase glucuronide excretion and levels in urine; therefore, decreased concentration of melatonin glucuronide is the direct evidence of decreased levels of melatonin. 1 UNIPROT:P17948 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9ff699fa-ca00-11e5-be63-001a4ae51246 15695787 "FLT catabolism primarily occurs in the liver to produce a glucuronide conjugate, which is exported to the blood and eventually is cleared by the kidneys (19,20).18F-FLT and18F-FLT-glucuronide metabolite appears to be the only observed labeled species in blood during the imaging studies." 1 UNIPROT:O60760 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 8474d036-3905-11e8-a51f-001a4a160176 PMC5615117 Glutathione-S-transferase (GST) mediates glucuronide conjugation, a detoxification step of chemical intermediates excretion procedure[25]. 1 CHEBI:23053 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical cd908d92-bc47-11e5-ac4e-001a4ae51246 PMC2802066 Catechin extraction from 100μL of rat plasma was initiated by addition of 1mL of enzyme solution (250 U β-glucuronidase with sulfatase activity in 0.4M NaH2PO4pH 4.5) to degonjugate glucuronide and sulfate metabolites. 1 CHEBI:8988 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a2253df0-c9fe-11e5-9b70-001a4ae51247 15100172 SN-38 is inactivated by glucuronidation to form SN-38 glucuronide (SN-38G). 1 CHEBI:8988 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical ae946a1c-997f-11e9-bfff-001a4a160175 PMC6373181 Irinotecan is metabolized by carboxylesterase to form an active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), which, in turn, is inactivated by glucuronidation by UDP-glucuronyltransferase 1A1(UGT1A1) to yield SN-38 glucuronide (SN-38G) [8,9]. 1 MESH:D010636 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 374ba500-bc02-11e5-8abe-001a4ae51246 10.1016/j.foodchem.2012.07.085 It has been previously reported that an increase in the dose of olive oil phenols dose-dependently raised the concentration of glucuronide conjugates of hydroxytyrosol and tyrosol in urine (Miró-Casas et al., 2003; Salvini et al., 2006; Visioli et al., 2000). 1 MESH:D005480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d09821b8-ca01-11e5-b88f-001a4ae51247 15843492 Biosynthesis of Sulindac, Sulindac Sulfone, Indomethacin, Diclofenac, Flurbiprofen, Ketoprofen, and Naproxen Glucuronide Standards.HLMs have been used previously to produce authentic glucuronide standards (Soars et al., 2002). 1 UNIPROT:P20585 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein c90c5712-bbfa-11e5-8abe-001a4ae51246 10.1016/j.addr.2012.09.027 In analogy with MRP1, MRP3 may also contribute to a toxicological defense function, by eliminating a range of toxic organic anions, notably glucuronide conjugates, from various epithelial cell types. 1 UNIPROT:P20585 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 346e4192-c8de-11e5-9ad8-001a4ae51247 17121932 MRP1 has also been shown to mediate efflux of sulfate, glucuronide, and glutathione conjugates, such as estradiol 17-(β-d-glucuronide) (E217G) and cysteinyl leukotriene C4(LTC4; refs.14,19). 1 UNIPROT:P20585 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 2c27b1de-cbf0-11e5-b7d4-001a4ae51246 10329726 MRP1 accepts many conjugates as substrates such as glutathione conjugates (e.g.2,4-dinitrophenyl-S-glutathione (DNP-SG), glutathione disulfide, and leukotriene C4(LTC4)), glucuronide conjugates (e.g.17β estradiol-17β-d-glucuronide (E217βG)), and sulfated conjugates of certain bile acids (e.g.3α-sulfatolithocholyltaurine) (1-3). 1 UNIPROT:P22310 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a57febc2-c47b-11e5-9cc6-001a4ae51246 21673130 "From the tested UGTs, only UGT1A9, UGT1A4, UGT2B7, UGT2B4, and UGT2B17 produced significant amounts of eslicarbazepine glucuronide." 1 UNIPROT:P22310 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 531bb2aa-bc45-11e5-9b9d-001a4ae51247 PMC1779459 As shown in a concentration curve for both isoforms of 4-OH-TAM (Figure4), the rate of UGT1A4-catalyzed glucuronide formation was fully saturated at approximately 10–15 μM fortrans-4-OH-TAM andcis-4-OH-TAM in our assay conditions. 1 CHEBI:310312 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 1 UNIPROT:P06133 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein b5178d2a-c47a-11e5-91a7-001a4ae51247 PMC3205324 Kaempferol formed three glucuronides (5-O, 7-O, and 4′-O) with the exception of reactions promoted by UGT1A4, UGT2B15, and UGT2B17 which resulted in no products, UGT1A7 which yielded only two products, and UGT2B4 which led to only one glucuronide. 1 UNIPROT:P06133 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a57febc2-c47b-11e5-9cc6-001a4ae51246 21673130 "From the tested UGTs, only UGT1A9, UGT1A4, UGT2B7, UGT2B4, and UGT2B17 produced significant amounts of eslicarbazepine glucuronide." 1 UNIPROT:P06133 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 5fd0f008-c471-11e5-9cc6-001a4ae51246 19126757 In humans, UGT2B4 mediates glucuronide conjugation at the 6α-hydroxy position while UGT2B7 transfers glucuronosyl moieties to 3α- and 6α-hydroxy groups (87,244,320). 1 UNIPROT:P35503 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 81eda5d8-3548-11e8-a51f-001a4a160176 18565494 In this study, one more glucuronide was produced by recombinant UGT1A3 (Fig. 3e) than UGT1A9 (Fig. 3e′), indicating other UGTs besides UGT1A9 may participate in some flavonoid metabolisms. 1 UNIPROT:P35503 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 25e7e190-3aa2-11e8-a34b-001a4a160175 25684194 2, only the major UGT1A3-mediated glucuronide was detected at the exact mass of 567.3170m/zunder the reported incubation conditions. 1 UNIPROT:P35503 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3ad13b72-ca5d-11e5-8050-001a4ae51246 12920167 "Within group B both enzymes of the 2B subfamily, 2B4 and 2B7, glucuronidated this substrate, whereas only UGT1A3 of the 1A subfamily produced detectable amounts of glucuronide-conjugated 5β-EPIM (Table 4)." 1 MESH:D006859 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 3760c228-c8e6-11e5-a1fd-001a4ae51246 17998299 "The quantitation was accomplished by comparing the absolute integral values of a well resolved proton signal in each glucuronide sample to the integral of the same signal in an external standard (1′-hydroxymidazolam)." 1 MESH:D006859 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 4684e531-361b-11eb-88c9-001a4a160176 PMC7729672 According to HMBC spectra, δ4.90, which was the terminal hydrogen signal of glucuronide, related to the δ147.2 (C-2’), which indicated that glucuronide was linked to C-2’. 1 MESH:D006859 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c8f4a7e2-c470-11e5-9cc6-001a4ae51246 19910512 "In particular, the1H spectrum ofM5clearly showed the anomeric proton signal (4.37 ppm) of the glucuronide moiety, whereas the correlation spectroscopy spectrum indicated that this was the most downfield resonance in a five-proton spin system that terminated with a doublet at 3.59 ppm." 1 MESH:D005665 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d1a6002c-f518-11eb-9fab-001a4a160175 30225802 This percentage of intracorporeal metabolic clearance in AKI patients is consistent with the values reported in chronic renal patients, where approximately 40–50% of the administered furosemide dose was eliminated by renal metabolism to yield the glucuronide [10,23]. 1 MESH:D011339 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 8c3a621c-5c61-11e7-9fde-001a4ae51247 PMC5075059 "Probenecid inhibits zidovudine glucuronidation and renal excretion of the ether glucuronide metabolite 3′-azido-3′-deoxy-5′-β-d-glucopyranuronosylthymidine (GAZT), possibly via renal uptake, secretory transporters, a marked reduction in the urinary excretion ratio of GAZT to zidovudine, and a decrease in the renal clearance of GAZT after probenecid coadministration (13)." 1 CHEBI:2150 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 329976f4-7b8a-11ee-add2-0050569a791b 10.1007/s11845-023-03366-x DHT-reduced metabolite, 5α-androstane-3α,17β-diol glucuronide, is markedly elevated in idiopathic hirsutism with no significant androgenicity and reflects an increased 5α–reductase activity in these patients [16]. 1 UNIPROT:P10635 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 7b035fa0-e9d3-11e5-acc1-001a4ae51246 PMC4788153 The AUC24metabolite ratios of all CYP2D6-mediated metabolites (R,S-DHMA 3-sulfate,R,S-DHMA 4-sulfate,R,S-HMMA sulfate, andR,S-HMMA glucuronide) toR/S-MDMA were significantly different between placebo-pretreated CYP2D6 EMs and IMs and between placebo-pretreated EMs and bupropion-pretreated EMs but not between IMs and bupropion-pretreated EMs (Fig 6). 1 UNIPROT:A1Z6E0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 54bc6f6c-bc47-11e5-9b9d-001a4ae51247 PMC2646188 "The reaction catalyzed by β‐glucuronidase is, β‐D‐glucuronide + H2O → D‐glucuronate + alcohol." 1 UNIPROT:A1Z6E0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 58c658c6-c7d2-11ee-9aaa-0050569a1f61 10.1016/j.addr.2023.114902 In particular, irinotecan-induced gastrointestinal toxicities are mediated by gut bacterial β-glucuronidase (GUS), by cleaving glucuronide from the SN38G (inactive metabolite) and releasing SN-38 in the gastrointestinal tract. 1 UNIPROT:Q8TCC7 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a200ee56-c9fd-11e5-ab20-001a4ae51246 14762099 "These results suggest that OAT3/Roct accepts sulfate and glucuronide conjugates as a substrate, and is likely to be involved in renal excretion of those conjugates cooperating with OATv1." 1 UNIPROT:Q8TCC7 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein bc315422-3919-11e8-a51f-001a4a160176 21244849 Since isoflavone glucuronides are the main metabolites in humans[10], OAT3 may contribute to the urinary excretion of isoflavones by mediating the uptake of glucuronide conjugates from blood into proximal tubules. 1 PF:PF06725 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 54d2fc8a-352d-11e8-8636-001a4a160175 27417440 The 3D cell culture model also allowed the identification and quantification of Phase II glucuronide and sulfate conjugates of all hydroxylated NVP metabolites (Fig.4a). 1 CHEBI:63716 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical d98b82f8-c47d-11e5-85e4-001a4ae51246 PMC3028780 "Since only a small percentage (around 30%) of raltegravir excreted via the kidney is in the parent form, with the remaining 70% being the glucuronide metabolite (24), it is important to determine if the raltegravir glucuronide is also transported by SLC22A6 and inhibited by tenofovir." 1 CHEBI:32772 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 7ccaa7bc-bc38-11e5-8d2d-001a4ae51247 PMC3307704 The methoxy substitution for these hydroxyl groups on our lead compound2should prevent these glucuronide and sulfate additions and contribute to sustained bioactivity. 1 IP:IPR005331 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 500221e8-3793-11e6-8a17-001a4ae51247 PMC4930290 In fact, chrysin glucuronide and chrysin sulfate were mainly produced by UDP-glucuronosyltransferase (UGT) 1A1, and sulfotransferase (SULT) 1A3 and 1A1, respectively (Galijatovicet al., 1999;Walleet al., 2000). 1 IP:IPR005331 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily dd21a4ae-c9cb-11ee-ae05-0050569a1f61 10.1016/j.prmcm.2022.100190 The metabolism of FA is mainly caused by the enzyme sulfotransferase and uridine-5,1-diphtho-glucuronocyltransferase (UDP glucuronosyltransferase) in the liver with its major metabolite being sulphonyl glucuronide in plasma. 1 CHEBI:17256 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a9e6f436-c8df-11e5-a1fd-001a4ae51246 16751262 "Di-glucuronide of PA-457 (di-PA-457G,tR= 7.9 min) was identified by the main deprotonated molecular ion, 935m/z, and fragmentation ions, 759m/z, for the neutral loss of one glucuronide moiety (176 Da), 583m/zfor the neutral loss of double glucuronide moieties (2 × 176 Da), and 455m/zfor the following cleavage of betulinic acid." 1 CHEBI:17256 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical f8c5303a-c467-11e5-91a7-001a4ae51247 23455671 The important ion atm/z423 [M−H−168−194]−was assigned to a sequential loss of an RDA fragment (168 Da), a water molecule (18 Da) and a loss of a glucuronide moiety (176 Da). 1 CHEBI:28870 methylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical ed2a291c-3533-11e8-9fbf-001a4a160176 21371557 EGC glucuronide, methylated EGC glucuronide, methylated EGC sulfate, EC glucuronide, EC sulfate, methylated EC sulfate, as well as the glucuronide and sulfate metabolites of the ring fission metabolites of tea catechins, M4, M6 and M6′, were the major human urinary metabolites of tea polyphenols. 1 CHEBI:28870 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 3d30b014-3522-11e8-8f56-001a4a160175 23835414 Phase II metabolites of ibuprofen The ion peak attR16.0min gave am/zof 381.1556 (peak 4), which corresponds to the mass of acyl glucuronide of IBF, while them/z397.1512±0.0001 recorded for the peaks eluting attR10.0–11.9min (peaks marked with 5) and at peak attR1.6min (peak 6) corresponded to the mass of the acyl glucuronide of hydroxylated IBF or ether glucuronide of hydroxylated IBF. 1 CHEBI:28870 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 730f1ace-bc3c-11e5-9b9d-001a4ae51247 PMC4055232 Extracted ion chromatograms (EICs) ofm/z283.1540 for QHS and monohydroxylated deoxy-QHS,m/z284.1856 for deoxy-QHS,m/z316.1775 for monohydroxylated QHS,m/z332.1704 for dihydroxylated QHS,m/z476.2126 for the glucuronide of monohydroxylated deoxy-QHS,m/z492.2076 for the glucuronide of monohydroxylated QHS, andm/z316.2118 for ARM (the internal standard; IS), with a 5 ppm range centred on the exactm/zvalue were generated for quantitation. 1 CHEBI:28870 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1d57c780-377c-11e8-87fd-001a4a160176 19362796 The fragment ion atm/z374 (374=198+176) was the glucuronide conjugated benzoyl moiety and it further produced the ions atm/z198 and 170 by losses of glucuronide and CO, respectively. 1 CHEBI:28870 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 13765aa4-cb29-11e5-8189-001a4ae51246 11408365 "A species difference in biliary metabolite profile existed in that bexarotene acyl glucuronide was the predominant metabolite in rat, while in dog the major metabolite was hydroxylated bexarotene acyl glucuronide." 1 CHEBI:28870 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1e3d7554-d049-11ec-99c8-0050569a791b PMC8577747 It is mostly hydroxylation of the 2-methyl group (2-hydroxymetronidazole), oxidation of the 1-ethyl group (1-metronidazole acetic acid) and glucuronide conjugation of hydroxylated metabolite (metronidazole glucuronide) (Fig 1). 1 PUBCHEM:11228183 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 2659a1f2-c47c-11e5-9da3-001a4ae51247 PMC3242074 Synergy between ABT-737 and conventional cytotoxic agents in normoxia has been reported in a range of adult tumor types (21), and ABT-737 is able to reverse 13-cis-retinoic acid-induced resistance to cytotoxic agents in neuroblastoma cell lines (38). 1 CHEBI:80845 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 1 CHEBI:75718 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 1 MESH:D009369 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 166e3c90-c471-11e5-85e4-001a4ae51246 19372567 "Targeted expression or antibody-mediated accumulation of βG in tumors can also enhance the antitumor activity of exogenously administered glucuronide prodrugs (19–22)." 1 MESH:D009569 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 77a7109c-c8de-11e5-a1fd-001a4ae51246 16621933 "A novel finding of our study is that both NO donors significantly reduced the formation of the glucuronide conjugates of DEM metabolites (i.e., DOR and HOM) (Fig. 5)." 1 CHEBI:18332 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1e100e8c-3554-11e8-8f56-001a4a160175 19150343 T4 glucuronidation (carried out by UGT1A1 and 1A3) leads to a stable T4 glucuronide which may serve as a mechanism of delivery of T4 into intracellular compartments, as discussed in Section5.1[51,52]. 1 FPLX:CYP activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 5d9dfff8-341b-11e8-8636-001a4a160175 19646518 Besides the phosphorylation of AZT through thymidine kinase and other kinases, leading to production of monophosphate, diphosphate and triphosphate, AZT glucuronide and 3′-amino-3′-deoxythymidine (AMT) are also produced by glucuronyl transferase and CYP450/P450-reductase, respectively (Veal and Back, 1995). 1 FPLX:CYP activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 7911602a-3760-11e8-a34b-001a4a160175 21920188 Ethinyl-estradiol is metabolized primarily by 2-hydroxylation catalyzed by cytochrome P-450 3A4 before conjugation to an inactive glucuronide and excreted primarily in the urine[17,18]. 1 UNIPROT:P31944 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 2bbc3a62-c8df-11e5-9cb8-001a4ae51247 16988054 "Mice lacking Mrp3 exhibited normal unconjugated bile salt transport but decreased serum concentrations of glucuronide conjugates of bile acids (Zelcer et al., 2006)." 1 MESH:D014529 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 5a4975d8-bc15-11e5-8abe-001a4ae51246 PMC2877023 AASs are commonly excreted in urine mainly as glucuronide conjugates, the formation of which is catalyzed by various uridine diphosphate-glucuronosyltransferase (UGT) enzymes. 1 MESH:D014529 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 4d377582-f577-11eb-84b5-001a4a160175 PMC7395045 Independent investigations also support the key role of the acyl glucuronide produced by uridine diphosphoglucuronosyl transferase as a molecular initiation event (Oda et al.56; Seitz and Boelsterli79), and among NSAIDs the salicyl acyl glucuronide derived from aspirin is a further example. 1 MESH:D012176 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 2d113e39-f58b-11eb-94cf-001a4a160176 30790712 Discussion In the current work, we found lasting effects at PND30 following gestational exposure to BPA, including: increased retinoid-dependent signalling changes involving increasedRar γ,Rxr γandFgf21(BPA10), but reducedRxr βexpression (BPA100); induced ATRA biosynthesis based on its hepatic concentrations and expressions ofAdh1,Aox1andCyp1a2; and modulation of transporter expressions, includingMrp3andBcrptowards the biliary excretion of glucuronide metabolites. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily f2d02dc0-351b-11e8-87fd-001a4a160176 PMC5770198 This implied that when flavone 6-hydroxylase was downregulated, its substrate, chrysin, accumulated and was converted by a glycosyl transferase to produce chrysin glucuronide. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily c7dfadfa-ca5d-11e5-9088-001a4ae51247 12975337 The second step involves blocking the dissociation of CO2from parent drug by glucuronide conjugation, catalyzed by UDP-glucuronosyl transferase in the presence of UDPGA as a cofactor. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 166a18c5-f58b-11eb-8c06-001a4a160175 30770151 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 2e927e53-dc45-11ea-a2af-001a4a160175 30770146 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 135c2402-f58b-11eb-8c06-001a4a160175 30770150 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 4d377582-f577-11eb-84b5-001a4a160175 PMC7395045 Independent investigations also support the key role of the acyl glucuronide produced by uridine diphosphoglucuronosyl transferase as a molecular initiation event (Oda et al.56; Seitz and Boelsterli79), and among NSAIDs the salicyl acyl glucuronide derived from aspirin is a further example. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 1ec64878-f58b-11eb-8c0e-001a4a160175 30770149 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 IP:IPR003480 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 5d9dfff8-341b-11e8-8636-001a4a160175 19646518 Besides the phosphorylation of AZT through thymidine kinase and other kinases, leading to production of monophosphate, diphosphate and triphosphate, AZT glucuronide and 3′-amino-3′-deoxythymidine (AMT) are also produced by glucuronyl transferase and CYP450/P450-reductase, respectively (Veal and Back, 1995). 1 MESH:D005473 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 3d011e34-c8c0-11ee-b346-0050569a791b 10.1016/j.jwpe.2023.103490 For instance, fluoxetine “an antidepressant” medicine, approximately 20–30 % is metabolized in the human body to produce the (norfluoxetine and fluoxetine glucuronide) metabolites, while the remaining is passed unaltered to sewage systems[119]. 1 UNIPROT:O75469 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 357ef054-bc40-11e5-8abe-001a4ae51246 PMC3208783 Importantly, PCN stimulation of PXR decreased the urinary excretion of α-CEHC glucuronide and γ-CEHC glycoside in wild-type but not PXR-null mice. 1 UNIPROT:O75469 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 65d39f32-c471-11e5-91a7-001a4ae51247 PMC2666179 In summary, using the combination of metabolomic analysis and genetically modified mouse models, a novel vitamin E metabolite, γ-CEHC Glc, was identified activated PXR was found to significantly lower the concentration of the α-CEHC glucuronide and γ-CEHC Glc in wild-type but not inPxr-null mice. 1 MESH:D000077146 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 58c658c6-c7d2-11ee-9aaa-0050569a1f61 10.1016/j.addr.2023.114902 In particular, irinotecan-induced gastrointestinal toxicities are mediated by gut bacterial β-glucuronidase (GUS), by cleaving glucuronide from the SN38G (inactive metabolite) and releasing SN-38 in the gastrointestinal tract. 1 UNIPROT:O95613 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 357ef054-bc40-11e5-8abe-001a4ae51246 PMC3208783 Importantly, PCN stimulation of PXR decreased the urinary excretion of α-CEHC glucuronide and γ-CEHC glycoside in wild-type but not PXR-null mice. 1 UNIPROT:P02814 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 34d41702-ca5e-11e5-a3f7-001a4ae51246 12815171 "In rats, PB treatment significantly impaired the biliary excretion of the glucuronide metabolites of morphine (Roerig et al., 1974), valproic acid (Watkins and Klaassen, 1982), and acetaminophen (Brouwer and Jones, 1990;Studenberg and Brouwer, 1992)." 1 UNIPROT:P20813 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 663be846-5c5d-11e7-9833-001a4ae51246 PMC5075090 The monohydroxymetabolites can be hydroxylated by CYP2B6 to dihydroxymetabolites (29) or conjugated to glucuronide and/or sulfate metabolites (28,48), with subsequent excretion in urine (37). 1 MESH:D014535 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c7dfadfa-ca5d-11e5-9088-001a4ae51247 12975337 The second step involves blocking the dissociation of CO2from parent drug by glucuronide conjugation, catalyzed by UDP-glucuronosyl transferase in the presence of UDPGA as a cofactor. 1 MESH:D014535 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 6b966044-cb8d-11e5-8106-001a4ae51247 11124229 "UDPGA (50 μM) assays allow higher levels of radiolabel incorporation into the glucuronide, which enhances assay sensitivity making this a useful tool for screening." 1 MESH:D016859 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d5c80208-c47e-11e5-8491-001a4ae51247 PMC2888634 Sulindac sulfide (a COX-1 and COX-2 inhibitor), sulindac sulfone (exisulind, a proapoptotic agent that does not inhibit COX), and nordihydroguaiaretic acid (a lipoxygenase inhibitor) each inhibited growth of NSCLC and SCLC cell lines, and were synergistic with paclitaxel, cisplatin, and 13-cis-retinoic acid[426]. 1 MESH:D013792 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 63a50e76-c8e0-11e5-9624-001a4ae51246 16815871 "Coadministered thalidomide for 1 or 5 days significantly reduced the biliary excretion of CPT-11, SN-38, and SN-38 glucuronide." 1 MESH:D002264 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype a5bd0a4c-375c-11e8-a34b-001a4a160175 24835592 During hepatic metabolism, DCF undergoes hydroxylation to yield predominantly 4′-hydroxydiclofenac (4′-OH-DCF) and to minor extent 5-hydroxydiclofenac (5-OH-DCF), as well as glucuronidation of the carboxylic acid to produce the 1-O-acyl glucuronide (DCF-gluc) (see Table S-1 for structures)[3]. 1 CHEBI:89981 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a961953a-bbfa-11e5-9b9d-001a4ae51247 PMC3963113 Also endotoxin, an active component in the outer membrane of the gram negative bacteria, decreases the biliary excretion of sparfloxacin and its glucuronide probably due to impairment of their hepatobiliary transport systems and renal handling [33]. 1 CHEBI:17245 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1d57c780-377c-11e8-87fd-001a4a160176 19362796 The fragment ion atm/z374 (374=198+176) was the glucuronide conjugated benzoyl moiety and it further produced the ions atm/z198 and 170 by losses of glucuronide and CO, respectively. 1 UNIPROT:Q9HAW9 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 91921d3e-bc00-11e5-8abe-001a4ae51246 PMC5470586 Interestingly, both UGT1A8 and UGT1A10 produced a significant amount of a different 3′-O-methyl-epicatechin glucuronide (76% and 58% respectively compared to the amount of the desired product synthesized with UGT1A9) (Supplementary Table 2, peak5). 1 UNIPROT:Q9HAW9 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3f730ed2-bc41-11e5-ac4e-001a4ae51246 10.1016/j.trim.2013.05.005 Bernard et al.[30]suggested that the UGT1A8 isoform might contribute to the glucuronide levels and to a lesser extend the AcMPAG levels. 1 UNIPROT:Q9HAW9 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 94d0dfda-351b-11e8-a34b-001a4a160175 28246004 Contribution of UGTs to the glucuronidation of genistein in liver and kidney A panel of recombinant human UGTs was used to screen for the glucuronidation of genistein using our previous published data[21], which proved that UGT1A1, UGT1A8, UGT1A9, and UGT1A10 produced a significant amount of glucuronide metabolite (Fig. 2A). 1 FPLX:GST activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 8474d036-3905-11e8-a51f-001a4a160176 PMC5615117 Glutathione-S-transferase (GST) mediates glucuronide conjugation, a detoxification step of chemical intermediates excretion procedure[25]. 1 MESH:D011355 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 9ed04bde-cb27-11e5-8189-001a4ae51246 11160851 "A common issue in prodrug monotherapy and antibody-directed enzyme prodrug therapy is bioactivation of the glucuronide prodrug by β-glucuronidase." 1 UNIPROT:Q99707 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 4828ede4-bc1e-11e5-8abe-001a4ae51246 10.1016/j.jchromb.2010.01.042 Every method presents different strengths and limitations, For example, LC–MS methods enable the direct analysis of the glucuronide and sulphate conjugates of the metabolites without need of previous hydrolysis of the samples as long as reference standards of the conjugates are available for quantification[31]. 1 UNIPROT:Q99707 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 2f22d7ce-bc1e-11e5-9b9d-001a4ae51247 10.1016/j.jchromb.2008.09.017 MS–MS neutral loss scan analysis enabled determination of glucuronide and sulfate conjugates by monitoring loss of 176 and 80Da[24], respectively, and facilitated the characterization of metabolic profile of nitazoxanide in goats. 1 MESH:D001564 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 4a66cf6f-dc88-11ea-8b9c-001a4a160176 PMC6309585 Compared to BaP alone treatment, RVT + BaP and RVT prior to BaP treatment induced the production of more glucuronide metabolites.Fig. 1 MESH:D014530 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 166a18c5-f58b-11eb-8c06-001a4a160175 30770151 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 MESH:D014530 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 1bb0975c-ae94-11ec-ae7b-0050569a1f61 PMCPMC8778816 BPA glucuronide is driven by uridine diphosphate glucuronosyltransferases (UGTs) in the liver and gut. 1 MESH:D014530 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype dd21a4ae-c9cb-11ee-ae05-0050569a1f61 10.1016/j.prmcm.2022.100190 The metabolism of FA is mainly caused by the enzyme sulfotransferase and uridine-5,1-diphtho-glucuronocyltransferase (UDP glucuronosyltransferase) in the liver with its major metabolite being sulphonyl glucuronide in plasma. 1 MESH:D014530 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 135c2402-f58b-11eb-8c06-001a4a160175 30770150 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 MESH:D014530 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 2e927e53-dc45-11ea-a2af-001a4a160175 30770146 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 MESH:D014530 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 1ec64878-f58b-11eb-8c0e-001a4a160175 30770149 Glucuronidation is facilitated by UDP glucuronyl transferase, which leads to the transfer of a glucuronic acid functional group (GA) from UDP-glucuronic acid (UDP-GA) to the hydroxyl group of TFM or that found on the chlorophenol ring of niclosamide, yielding the respective glucuronide conjugates. 1 IP:IPR005556 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 38b398e6-5c0e-11e7-b83b-001a4ae51246 PMC5464342 Our assay was not designed to identify phase II metabolites suggesting that the two additional peaks observed in the previous study may correspond to conjugated metabolites, such as the 17β‐DHE‐glucuronide produced by UGT2B17 (Sun et al.2010). 1 FPLX:Acetyl:CoA:synthetase inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 6a3287d4-ca00-11e5-ab20-001a4ae51246 PMC1747102 36 In blood no effect from smoke inhalation has been observed on GSH.59However, ACS decreased the antioxidants methylumbelliferone glucuronide and ferroxidase35,62and increased lipid peroxide and 8-epi-PGF2α, markers of lipid peroxidation in blood. 1 MESH:D002995 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d74caa92-cbf0-11e5-b7d4-001a4ae51246 9918540 "Reduced clofibric acid clearance in the presence of probenecid, in rabbits and humans, has been suggested to be due to competitive inhibition of the renal membrane transport of clofibric acid glucuronide, leading to reduced renal clearance and increased systemic hydrolysis to the aglycone (Meffin et al., 1983a)." 1 CHEBI:24298 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical ba4adf94-dcc7-11ea-a68b-001a4a160175 PMC6153689 Additionally, glucuronic acid and presumably dysregulation of glucuronide-related detoxification systems have been found to be deeply involved in the pathogenesis of jaundice. 1 UNIPROT:P16662 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 2792e8e6-c466-11e5-a92e-001a4ae51246 23288867 "In the case of 16-epiestriol, NMR analysis of the main glucuronide produced by UGT2B7 detected only a single correlation, between the anomeric proton and C16 of 16-epiestriol (Table 1)." 1 UNIPROT:P16662 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 834dc114-c9fd-11e5-be63-001a4ae51246 14977865 Diclofenac (500 μM) was found to be a potent inhibitor of benzylic glucuronide formation by UGT2B7 (Table 5) with an IC50value of 52.7 μM. 1 UNIPROT:P16662 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a57febc2-c47b-11e5-9cc6-001a4ae51246 21673130 "From the tested UGTs, only UGT1A9, UGT1A4, UGT2B7, UGT2B4, and UGT2B17 produced significant amounts of eslicarbazepine glucuronide." 1 UNIPROT:P16662 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a2df9c38-c466-11e5-91a7-001a4ae51247 PMC3837878 "DHA, in turn, undergoes glucuronide conjugation mediated by UGT2B7 and UGT1A9." 1 MESH:D000077157 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype a1612518-c7cb-11ee-9aaa-0050569a1f61 10.1016/j.pharmthera.2023.108459 Given the apparent predominant roles of P-gp in irinotecan transport, BCRP and P-gp in SN-38 disposition, and BCRP in SN-38 glucuronide efflux (Fig. 5) (Parvez et al., 2021), lapatinib, pazopanib, regorafenib and sorafenib may potentially variably perturb the disposition of SN-38 and SN-38 glucuronide (and the SN-38 to SN-38 glucuronide plasma AUC ratio). 1 MESH:D000077610 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 13765aa4-cb29-11e5-8189-001a4ae51246 11408365 "A species difference in biliary metabolite profile existed in that bexarotene acyl glucuronide was the predominant metabolite in rat, while in dog the major metabolite was hydroxylated bexarotene acyl glucuronide." 1 CHEBI:64212 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical d09821b8-ca01-11e5-b88f-001a4ae51247 15843492 Biosynthesis of Sulindac, Sulindac Sulfone, Indomethacin, Diclofenac, Flurbiprofen, Ketoprofen, and Naproxen Glucuronide Standards.HLMs have been used previously to produce authentic glucuronide standards (Soars et al., 2002). 1 CHEBI:8633 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 05423cd8-bc1e-11e5-9b9d-001a4ae51247 10.1016/j.jchromb.2013.05.016 Due to the change in hemodynamics, the reduced concentration of puerarin or UGTs in the blood of the blood stasis rats might reduce the glucuronide formation of puerarin. 1 UNIPROT:Q9HAW8 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 6f745238-c47c-11e5-8491-001a4ae51247 PMC3251030 The primary fragment ion of theR-7-hydroxywarfarin glucuronide produced by UGT1A10 wasm/z325 rather than 355 (Fig. 4E). 1 UNIPROT:Q9HAW8 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 94d0dfda-351b-11e8-a34b-001a4a160175 28246004 Contribution of UGTs to the glucuronidation of genistein in liver and kidney A panel of recombinant human UGTs was used to screen for the glucuronidation of genistein using our previous published data[21], which proved that UGT1A1, UGT1A8, UGT1A9, and UGT1A10 produced a significant amount of glucuronide metabolite (Fig. 2A). 1 UNIPROT:Q9HAW8 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 91921d3e-bc00-11e5-8abe-001a4ae51246 PMC5470586 Interestingly, both UGT1A8 and UGT1A10 produced a significant amount of a different 3′-O-methyl-epicatechin glucuronide (76% and 58% respectively compared to the amount of the desired product synthesized with UGT1A9) (Supplementary Table 2, peak5). 1 CHEBI:28821 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 222b49fa-3900-11e8-87fd-001a4a160176 26201645 The results indicated that piperine increased theCmaxand AUC of emodin as well as decreasing the AUC andCmaxof emodin glucuronide, which is evidence that piperine may reduce glucuronidation of emodin and enhance its bioavailability. 1 CHEBI:28821 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1e9373b4-ea2d-11ee-b22c-0050569a1f61 10.1016/j.biopha.2022.113555 The results revealed that piperine increased the plasma emodin concentration and decreased the concentration of emodin glucuronide, hence, indicating a marked inhibition of UGTs[29]. 1 PF:PF03646 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 3aa8b3ee-ab96-11e6-9646-001a4ae51246 26276581 Thus, the objective of this study was to develop a fast, robust and predictive screening method to rank and flag compounds on the basis of their acyl glucuronide reactivity without synthesizing the 1-O-β-acyl glucuronide authentic standard. 1 PF:PF02893 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily e3a635bc-c47d-11e5-91a7-001a4ae51247 PMC3043622 One gram of acetaminophen was given at ∼0630 and repeated at ∼0845 to enable measurement of urinary glucuronide. 1 PF:PF09213 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily c8eb3dee-c8e7-11e5-9ad8-001a4ae51247 17537869 "However, if the 12-hydroxyl group were the site of glucuronidation, then oxidation products of tigecycline glucuronide (M3) would be expected." 1 UNIPROT:P02786 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9278ddaa-c8df-11e5-a1fd-001a4ae51246 16772539 "In this study, the absence of intestinal and hepatic Mrp2 in our TR-negative rats resulted in manyfold increased serum glucuronide concentrations, a significantly increase of urinary excretion at unchanged renal clearance, and a nearly abolished intestinal clearance." 1 FPLX:RAR activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 2b6cc8b8-bc11-11e5-8abe-001a4ae51246 10.1016/j.jnutbio.2011.04.010 Treatment with an HDACi induced acetylation in RARβ2 hypermethylated promoters in the presence of 13-cis-retinoic acid, leading to reexpression of RARβ2 in RARβ2-negative, retinoid-resistant melanoma cells[21]. 1 MESH:D003975 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype a1530340-3526-11e8-b868-001a4a160176 23122274 Application to real samples As it was mentioned before, the objective of this study was to investigate whether the detection window of diazepam could be prolonged by directly detecting its glucuronide conjugates. 1 UNIPROT:P08684 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 10483c80-c467-11e5-8491-001a4ae51247 24366904 "These studies indicated that rifampicin (a known potent CYP3A4 inducer) moderately increased formation of M2a, M2b, and faldaprevir glucuronide, consistent with the clinical observation of increased faldaprevir clearance by another inducer, efavirenz (Kiser et al., 2013)." 1 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 01887c0e-ca03-11e5-be63-001a4ae51246 15944213 "Studies have shown that the detoxification of certain cooked-food-derived carcinogenic HAs is highly dependent on UGT1A-mediated glucuronide conjugation (1,6–8)." 1 UNIPROT:P22309 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 94d0dfda-351b-11e8-a34b-001a4a160175 28246004 Contribution of UGTs to the glucuronidation of genistein in liver and kidney A panel of recombinant human UGTs was used to screen for the glucuronidation of genistein using our previous published data[21], which proved that UGT1A1, UGT1A8, UGT1A9, and UGT1A10 produced a significant amount of glucuronide metabolite (Fig. 2A). 1 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein e493c3d8-352b-11e8-a51f-001a4a160176 PMC7671852 Because the retention time of M1 was close to that of M2, the obtained glucuronide metabolites catalyzed by UGT1A1 and 1A9 were further characterized by hydrolysis with β-glucuronidases. 1 UNIPROT:P22309 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ae946a1c-997f-11e9-bfff-001a4a160175 PMC6373181 Irinotecan is metabolized by carboxylesterase to form an active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), which, in turn, is inactivated by glucuronidation by UDP-glucuronyltransferase 1A1(UGT1A1) to yield SN-38 glucuronide (SN-38G) [8,9]. 1 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 6f745238-c47c-11e5-8491-001a4ae51247 PMC3251030 The spectrum for theR-7-hydroxywarfarin glucuronide produced by UGT1A1 resembled those ofR- andS-6-hydroxywarfarin andS-7-hydroxywarfarin glucuronides. 1 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 884bcba4-c8ed-11e5-9faa-001a4ae51247 PMC2615638 "The formation of MG5, the most abundant isoliquiritigenin glucuronide, was catalyzed by several UGTs but predominantly by UGT1A1 and UGT1A9 (Fig. 5)." 1 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3d7b475c-bc2d-11e5-ac4e-001a4ae51246 PMC3901587 This inhibitory property has an impact on the level of the UGT1A1-mediated transport form of bilirubin, the corresponding glucuronide. 1 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein d23836ac-da8d-11ee-8b99-0050569a1f61 10.1007/s11920-018-0881-3 Metabolites eliminated in the urine include two thirds of the total dose as S-MHD and one third as glucuronide conjugates probably mediated by UGT1A1 [21] Lamotrigine is a mild inducer. 1 UNIPROT:P22309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 17a9dcf0-c46b-11e5-8491-001a4ae51247 25122565 "On the other hand, chenodeoxycholic acid was mainly glucuronidated by UGT1A3, with UGT1A1 catalyzing glucuronide formation at only 7% of the UGT1A3 rate.Fallon et al. (2013b)recently reported that the average protein level of UGT1A1 is 4.5-fold higher than that of UGT1A3 in human liver microsomes (36.2 versus 8.0 pmol/mg protein)." 1 UNIPROT:P22309 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 934a113a-ca02-11e5-be63-001a4ae51246 16339389 "These experiments confirmed that UGT1A3 was the highest producer of fulvestrant-glucuronide, whereas UGT1A1, -1A4, and -1A8 also produced significant amounts of the glucuronide." 1 UNIPROT:O15438 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 25b1792e-ca02-11e5-be63-001a4ae51246 16177239 "Induction of Mrp3 (as seen with APAP) may help to limit intracellular accumulation of glucuronide conjugates as well as bile acids in hepatocytes (Zelceret al., 2003b)." 1 UNIPROT:O15438 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 5291659a-cb28-11e5-9aa0-001a4ae51247 11306690 "The transport properties of MRP1 and 2 are different from those of Mrp3 in that the former accept both glutathione conjugates and glucuronide conjugates as good substrates (Suzuki and Sugiyama, 1998;Cui et al., 1999), whereas the latter accepts only glucuronide conjugates as good substrates (Hirohashi et al., 1999)." 1 UNIPROT:O15438 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 1180c156-c473-11e5-8491-001a4ae51247 19628752 "It should be noted that Mrp3 in the enterocytes could contribute to the differences in plasma levels of the glucuronide conjugates determined in addition to Mrp3 in the liver because the parent drugs were given orally, and glucuronidation also occurs in the small intestine (Grams et al., 2000) where Mrp3 is expressed in the basolateral membrane (Rost et al., 2002;Shoji et al., 2004;Zelcer et al., 2006)." 1 UNIPROT:O15438 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a8a25bd0-c9ff-11e5-9b70-001a4ae51247 15217779 By using membrane vesicles isolated from rat Mrp3-transfected cells, we have previously reported that Mrp3 preferentially accepts glucuronide conjugates such as E217βG and E3040 glucuronide and sulfated and monovalent bile acids rather than gutathione-conjugates, which is consistent with the present observations in BLMVs (Figs. 1 UNIPROT:O15438 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 2bbc3a62-c8df-11e5-9cb8-001a4ae51247 16988054 "Mrp2-deficient rats, and to a lesser extent Mrp2 knockout mice, have increased hepatic expression of Mrp3 (Hirohashi et al., 1998;Nezasa et al., 2006) and increased basolateral efflux of bilirubin glucuronides, acetaminophen glucuronide, the glucuronide conjugate of the steroid E3040, and 4-methylumbelliferyl glucuronide (Jansen et al., 1985;Takenaka et al., 1995;Xiong et al., 2000;Chu et al., 2006; Zamek-Gliszczynski et al.,2006a,c)." 1 UNIPROT:O15438 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 3df80406-3951-11e8-9192-001a4a160175 19426699 Mrp3) produce a more efficient basolateral secretion of the glucuronide and subsequent urinary elimination, as described by Allegaert et al. and Gelotte et al. 1 UNIPROT:O15438 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 24858d08-bc31-11e5-8d2d-001a4ae51247 PMC3777468 In recent reports, significant accumulation of etoposide glucuronide in the liver inMrp2−/−/Mrp3−/−mice was described, but neither single knockout showed this phenomenon, indicating an alternative pathway provided by Mrp2 and Mrp3 for hepatic elimination of etoposide glucuronide[80]. 1 UNIPROT:O15438 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein c90c5712-bbfa-11e5-8abe-001a4ae51246 10.1016/j.addr.2012.09.027 In analogy with MRP1, MRP3 may also contribute to a toxicological defense function, by eliminating a range of toxic organic anions, notably glucuronide conjugates, from various epithelial cell types. 1 UNIPROT:P46721 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ecd755e6-bee5-11e5-b74e-001a4ae51247 10.1016/j.tiv.2013.07.003 HepaRG cells have previously been shown to exhibit sinusoidal transport activity, especially NTCP-mediated uptake of taurocholate, OATP-mediated uptake of E3S, estradiol-17β glucuronide and pitavastatin, and OCT1-mediated uptake of TEA (Kotani et al., 2012; Le Vee et al., 2006; Szabo et al., 2013). 1 UNIPROT:P10632 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein ad6dfcb4-bcb4-11e8-b8fa-001a4a160176 PMC6137267 Furthermore, the formation of this metabolite required both NADPH and UDPglucuronic acid, leading to the conclusion that 3-hydroxydesloratadine was generated by a sequence involving initial N-glucuronidation, CYP2C8 hydroxylation of the glucuronide, and glucuronidase release of the 3-desloratadine metabolite (Figure 12). 1 UNIPROT:P10632 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 848fbaf6-ca01-11e5-b88f-001a4ae51247 16299161 "The marked increase in CYP2C8 inhibition caused by preincubating gemfibrozil glucuronide with human liver microsomes for 30 min was dependent on the presence of NADPH." 1 UNIPROT:P10632 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 51b3f342-ca5e-11e5-9088-001a4ae51247 12642475 "CYP2C8 is believed to mediate the metabolism of paclitaxel (Taxol), 9-cis-retinoic acid (Panretin), and 13-cis-retinoic acid (Accutane) (Parkinson, 1996;Mugford and Kedderis, 1998;Marill et al., 2002)." 1 UNIPROT:Q9Y6L6 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 341a5c70-8d8c-11e7-a20e-001a4ae51247 PMC5504478 An excellent example of this is highlighted in the article “Influence of OATP1B1 function on the disposition of sorafenib‐β‐D‐glucuronide” by Binset al.4This eloquent bench‐to‐bedside investigation builds upon previous mechanistic studies5by evaluating the clinical significance of inhibiting OATP1B1‐mediated transport of the glucuronide metabolite of sorafenib, sorafenib‐β‐D‐glucuronide (SG). 1 UNIPROT:Q9Y6L6 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein b4546244-3c6d-11f0-9ac3-0050569a1f61 10.1016/j.ejpb.2022.06.008 "In contrast, we found that hepatic overexpression of human OATP1B1, and perhaps OATP1B3, could partially rescue the altered pharmacokinetics of cintirorgon glucuronide in Slco1a/1b−/− mice." 1 UNIPROT:Q9Y6L6 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 03adc30a-c467-11e5-85e4-001a4ae51246 24346835 "This DDI is consistent with reduced enterohepatic cycling due to inhibition of ezetimibe glucuronide hepatic transport by OATP1B1 and possibly MRP2, as well as inhibition of intestinal efflux of both parent and glucuronide by P-gp and MRP2." 1 UNIPROT:Q9Y6L6 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein dbde4c98-3758-11e8-8f56-001a4a160175 27457785 Gemfibrozil and clopidogrel are highly associated with cerivastatin-induced rhabdomyolysis (Floyd et al., 2012), and they inhibited CYP2C8 irreversibly and hepatic OATP1B1 reversibly through their glucuronide conjugates (Shitara et al., 2004;Floyd et al., 2012;Tamraz et al., 2013). 1 CHEBI:25555 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical c240c60c-bbf0-11e5-9b9d-001a4ae51247 10.1016/S0960-894X(03)00466-9 Synthesis We attempted to synthesize the glucuronide and glucoside of WAY-123783 by the Mitsunobu procedure.11Phenolic OH and a nitrogen atom in the pyrazole ring of WAY-123783 were thought to be the reaction site. 1 CHEBI:6619 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 2c48e3a8-374c-11e8-a51f-001a4a160176 22982073 Nevertheless, compared with LTC4, MK-571 at higher concentrations could remarkably decrease the glucuronide efflux rate on both sides for either the A–B or the B–A direction. 1 UNIPROT:P09089 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 8b32d7fa-ae96-11ec-840e-0050569a791b PMCPMC8225184 Phase 2 metabolism of ZEN or ZEN Phase 1 metabolites by UDP-glucuronosyl transferases (UGTs) and sulfotransferases (SULTs) produces glucuronide and sulfate conjugates, respectively, that are secreted into bile or urine and thereby cleared from the body [33]. 1 UNIPROT:P09089 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a9505584-3404-11e8-a34b-001a4a160175 22521637 The concentration of glucuronides was calculated assuming that 1 mole of ZEN, β-ZEL and α-ZEL, respectively, produces 1mol of ZEN, β-ZEL, and α-ZEL glucuronide. 1 UNIPROT:O94956 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein f849f4c2-d3d2-11e5-888a-001a4ae51246 PMC4809317 One of the probable candidates for DCF-AG uptake would be OATP2B1, which is known to mediate uptake of glucuronide conjugates (Gao et al., 2012; Grosser et al., 2014). 1 MESH:D010455 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype b59dfa74-bc26-11e5-9b9d-001a4ae51247 10.1016/S0022-1759(01)00484-7 A pro-peptide can be synthesized by conjugating glucuronide to the amino terminus through the self-immolative linker(Rawale et al., 2001). 1 UNIPROT:P38936 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 1 IP:IPR005071 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily e6170866-ca00-11e5-be63-001a4ae51246 15917434 "The canalicular multidrug resistance protein 2 (rat Mrp2; Abcc2), a 190-kDa membrane glycoprotein located in the canalicular membrane, mediates the ATP-dependent excretion of a wide spectrum of organic anions into bile, including glutathione, glucuronide, and sulfate conjugates (Jansen et al., 1987;Paulusma et al., 1996;Konig et al., 1999;Gerk and Vore, 2002)." 1 MESH:D051379 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 82bdcb06-c47e-11e5-9da3-001a4ae51247 PMC2835398 "Mrp3 transports the glucuronide conjugate of resveratrol in vitro, and knockout mice lacking Mrp3 have reduced urinary and renal concentrations of resveratrol and its glucuronide conjugate (van de Wetering et al., 2009a)." 1 MESH:D051379 decreases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype e21ab4e6-c484-11e5-91a7-001a4ae51247 PMC3463821 "Although increased plasma glucuronide levels were probably also aided by increased glucuronidation rates in the knockout mice, altered distribution is the major reason for the very large percentage increases in plasma AUC of genistein conjugates." 1 UNIPROT:P14410 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein c8281e2c-c478-11e5-a92e-001a4ae51246 PMC3141883 "Age did not alter UGT regioselectivity toward quercetin in SI, whereas differential expression of UGT isoforms between segments could enable the formation of divergent glucuronide metabolite profiles." 1 UNIPROT:O43281 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 77f2c8a4-3388-11e8-a34b-001a4a160175 20385269 In patients with high-risk stage 3 NB, the 5-year EFS and the OS rates were increased using transplantation of autologous bone marrow or 13-cis-retinoic acid but at present follow-up there is no statistical significant difference in outcome when compared to a protocol using intensive chemoradiotherapy[12]. 1 UNIPROT:O00186 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 801b1b24-bc27-11e5-9b9d-001a4ae51247 10.1016/j.phymed.2011.06.002 Previous study in the rat showed that the phase II metabolites of paracetamol (glucuronide and sulphate) were significantly increased by PSP, which may reflect either phase II enzyme induction or a decrease rate of metabolism which utilized the phase I pathways (Yeung et al. 1995). 1 MESH:D019811 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c96a568e-c9fe-11e5-be63-001a4ae51246 14744939 "Incubation of this biosynthetic hydroxylamine with monkey liver microsomes and UDPGA produced a glucuronide that had HPLC, MS/MS, and1H NMR characteristics identical to those of the major metabolite of1isolated from monkey urine." 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 8062cdb0-5c40-11e7-8c5f-001a4ae51246 PMC5241710 "This process gives rise to a haptenized penicilloyl–protein adduct, which can elicit an immune response.274−276Alb was the major plasma protein found to react with AX in vitro.81A comprehensive study showed that Lys190, Lys199, Lys351, Lys432, Lys541, and Lys545 (Table S1,Supporting Information) were the major sites of reaction of AX with Alb ex vivo in plasma.81,277Interestingly, the sites of Lys adduction can vary widely between subjects treated with the structurally related β-lactam antibiotic benzylpenicillin and was found to form multiple adducts in vivo with Alb in human subjects at Lys190, Lys195, Lys432, and Lys541.278 Nonsteroidal Anti-inflammatory drugs (NSAIDS) UDP-glucuronosyltransferases (UGTs) are important conjugation enzymes and catalyze the glucuronidation of numerous drugs, endobiotics, and procarcinogens.279The UGT-mediated glucuronide (Gluc) conjugation of chemicals is generally considered as a mechanism of detoxication, and the Gluc conjugates are generally less biologically or chemically reactive than their parent compounds.85However, many carboxylic acid containing drugs including NSAIDS are metabolized by UGTs to form β-1-O-acyl glucuronides (AGs), which are able to form adducts with nucleophiles in proteins and may contribute to toxicity of NSAIDS.276Evidence for the covalent binding of AGs to Alb by MALDI TOF MS and by CID with a four-sector tandem mass spectrometer was provided by Ding et al.83,280Tolmetin glucuronide (TG) was shown to bind to Alb via transacylation reactions to form adducts with Lys residues via displacement of the glucuronic acid moiety." 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 562aa702-bc2d-11e5-8d2d-001a4ae51247 PMC3937997 SN-38 is further catalyzed into the inactive glucuronide derivative SN-38G by several hepatic and extrahepatic UGT enzymes. 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 500221e8-3793-11e6-8a17-001a4ae51247 PMC4930290 In fact, chrysin glucuronide and chrysin sulfate were mainly produced by UDP-glucuronosyltransferase (UGT) 1A1, and sulfotransferase (SULT) 1A3 and 1A1, respectively (Galijatovicet al., 1999;Walleet al., 2000). 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 25e7e190-3aa2-11e8-a34b-001a4a160175 25684194 UGT 1A4 produced this glucuronide and also levomedetomidine-N1-glucuronide, but its contribution was very low (Kaivosaari et al., 2008). 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily ac1aaa5e-3773-11e8-b868-001a4a160176 18977285 Therefore, it seems likely that glucuronide conjugation mediated by UGT is mainly responsible for the limited bioavailability of raloxifene in humans. 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 0434f6bc-c8eb-11e5-a4c6-001a4ae51246 PMC2664830 Glucuronide conjugation is often catalyzed by multiple UGT isozymes due to their broad substrate specificities. 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily c8281e2c-c478-11e5-a92e-001a4ae51246 PMC3141883 "Age did not alter UGT regioselectivity toward quercetin in SI, whereas differential expression of UGT isoforms between segments could enable the formation of divergent glucuronide metabolite profiles." 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 8f9b6b94-bc04-11e5-9b9d-001a4ae51247 PMC3234363 Hence, it is likely that the UGT that will mainly contribute to the formation ofent-17β-estradiol glucuronide in the human body will be UGT2B7. 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 5a4975d8-bc15-11e5-8abe-001a4ae51246 PMC2877023 AASs are commonly excreted in urine mainly as glucuronide conjugates, the formation of which is catalyzed by various uridine diphosphate-glucuronosyltransferase (UGT) enzymes. 1 FPLX:UGT activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily 0e82124a-c480-11e5-9da3-001a4ae51247 20304965 "Glucuronide conjugation is catalyzed by a family of UDP-glucuronosyltransferase (UGT) enzymes and occurs at nucleophilic functional groups containing oxygen (e.g., hydroxyl or carboxylic acid), nitrogen (e.g., amines), sulfur (e.g., thiols), and more rarely carbon (King et al., 2000)." 1 MESH:D001663 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c7f7b22e-c9fe-11e5-9b70-001a4ae51247 14744950 "At 100 μM concentration, bilirubin inhibited formation of the glucuronide from human liver microsomes and UGT1A4 Supersomes by 79.6% and 63.5%, respectively." 1 MESH:D009288 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d09821b8-ca01-11e5-b88f-001a4ae51247 15843492 Biosynthesis of Sulindac, Sulindac Sulfone, Indomethacin, Diclofenac, Flurbiprofen, Ketoprofen, and Naproxen Glucuronide Standards.HLMs have been used previously to produce authentic glucuronide standards (Soars et al., 2002). 1 UNIPROT:Q9Y3B2 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 1 MESH:D007660 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d09821b8-ca01-11e5-b88f-001a4ae51247 15843492 Biosynthesis of Sulindac, Sulindac Sulfone, Indomethacin, Diclofenac, Flurbiprofen, Ketoprofen, and Naproxen Glucuronide Standards.HLMs have been used previously to produce authentic glucuronide standards (Soars et al., 2002). 1 CHEBI:37924 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a799c950-bc3d-11e5-9b9d-001a4ae51247 PMC3516820 Finally, atazanavir, a protease inhibitor affecting glucuronidation, decreases the formation of raltegravir glucuronide and induces a moderate increase in raltegravir concentration [39,47]. 1 CHEBI:37924 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 20f1bb66-c47f-11e5-a92e-001a4ae51246 PMC2976128 "In summary, although atazanavir reduced the formation of the glucuronide metabolite, its steady-state boosting did not render a once-daily raltegravir dose of 400 mg pharmacokinetically similar to the standard twice-daily dose in terms of the concentration at the end of the dosing interval." 1 CHEBI:37924 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a1612518-c7cb-11ee-9aaa-0050569a1f61 10.1016/j.pharmthera.2023.108459 As might be expected for inhibition of hepatic raltegravir glucuronidation, atazanavir administration significantly reduced the plasma raltegravir glucuronide to raltegravir AUC ratio (Neely et al., 2010), and the elevation in the total serum bilirubin concentration frequently observed in study subjects further supports inhibition of UGT1A1 (Iwamoto, Wenning, Mistry, et al., 2008;Krishna, East, Larson, Valiathan, et al., 2016;Zhu et al., 2010). 1 CHEBI:30746 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 3a6610d4-e841-11e5-9207-001a4ae51246 PMC4766772 [35] Benzoyl glucuronide is produced by the reaction of benzoic acid with glucuronic acid, which accounts for 10–20% of benzoic acid elimination. 1 CHEBI:32114 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 3c50b01a-c8e9-11e5-a1fd-001a4ae51246 18474678 "A high concentration of salicylamide (1.5 mM) inhibited the formation of the glucuronide metabolites and did not inhibit the active transport of the four P450 inhibitors or the formation of 4-hydroxydiclofenac by recombinant CYP2C11." 1 UNIPROT:Q9LTH4 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein f6d56c5c-cb2b-11e5-8189-001a4ae51246 12386136 "Control experiments showed that BOA, a known β-oxidation inhibitor (Schulz, 1987), inhibited almost completely the three β-oxidation products of SVA as well as the glucuronide conjugate of B3, whereas only moderately (∼55%) inhibited the lactonization of SVA and minimally affected the CYP3A-mediated oxidative metabolites (Table2)." 1 MESH:D016572 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 94573c38-bbf7-11e5-8abe-001a4ae51246 PMC4658340 Cyclosporine has been shown to reduce the AUC of mycophenolic acid (MPA) by inhibiting its glucuronide conjugate mycophenolic acid glucuronide conjugate (MPAG) excretion into the bile. 1 MESH:D016572 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 69aa63c6-ced0-11ee-8b99-0050569a1f61 10.1007/s00467-018-3892-8 CsA inhibits the multidrug resistance protein 2-mediated transport of 7-O-MPA glucuronide into the bile, leading to less MPA exposure. 1 MESH:D016572 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 15def204-bc53-11e5-9b9d-001a4ae51247 PMC4683916 The concurrent use of tacrolimus may decrease the mycophenolic acid concentration, thereby leading to an increased dose of MMF.1718Contradictory results have also been reported, in that co-administration with cyclosporine required significantly higher doses of MMF to achieve similar mycophenolic acid levels as tacrolimus-treated patients.19It has also been suggested that the cyclosporine-mediated inhibition of the biliary excretion of mycophenolic acid glucuronide by the multidrug resistance-associated protein-2 transporter is the mechanism responsible for the interactions between cyclosporine and MMF. 1 MESH:D016572 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype a1612518-c7cb-11ee-9aaa-0050569a1f61 10.1016/j.pharmthera.2023.108459 (Conversely, cyclosporine administration reduces the enterohepatic recirculation of mycophenolic acid via inhibition of MRP2 as well as the hepatic uptake of the glucuronide by OATP1B1/3. 1 MESH:D016572 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 5090ece4-c8e8-11e5-9ad8-001a4ae51247 17954526 "Cyclosporin A increased the release of glucuronide and dihydroferulic acid in the basal compartment, suggesting that these two metabolites could also be effluxed to some extent to the apical side through the P-glycoprotein protein, localized on the apical side of enterocytes." 1 MESH:D016572 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 661c3fcc-ca01-11e5-be63-001a4ae51246 16272406 "In addition, they reported that CsA reduced the biliary excretion of the glucuronide metabolites of MPA by approximately 20%." 1 MESH:D000077185 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 64e0bd5c-c8e6-11e5-9ad8-001a4ae51247 17991766 "Resveratrol glucuronidation in the human liver is both regioselective and stereospecific, producing two major metabolites, resveratrol 3-O glucuronide (R3G) and resveratrol 4′-Oglucuronide (R4′G) (Aumont et al., 2001)." 1 MESH:D000077185 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 16a74ebc-bc20-11e5-9b9d-001a4ae51247 PMC4663613 Resveratrol inhibited production of apigenin glucuronide with aKivalue of 7.782 ± 0.84 μM. 1 MESH:D000077185 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype fcf4b7d8-bbdf-11e5-9b9d-001a4ae51247 PMC3399511 More than 70% of the resveratrol uptaked is absorbed and readily transformed to produce essentially sulphate and glucuronide derivatives [99]. 1 MESH:D004008 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 48f483e0-ca02-11e5-b88f-001a4ae51247 16129696 On the contrary, diclofenac only accepted the glucuronic acid from UDP-GlcA to form a glucuronide. 1 MESH:D004008 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 05b001ac-c8e7-11e5-9cb8-001a4ae51247 17220245 "In addition, diclofenac and indomethacin (both at 100 μM) inhibited the formation of glabridin glucuronide in rat hepatic and intestinal microsomes by 68.5 ± 15.2% and 72.3 ± 14.3%, respectively." 1 MESH:D004008 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d09821b8-ca01-11e5-b88f-001a4ae51247 15843492 Biosynthesis of Sulindac, Sulindac Sulfone, Indomethacin, Diclofenac, Flurbiprofen, Ketoprofen, and Naproxen Glucuronide Standards.HLMs have been used previously to produce authentic glucuronide standards (Soars et al., 2002). 1 MESH:D000470 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 3641c60a-5c31-11e7-8c5f-001a4ae51246 PMC5266722 All participants were required, and instructed as such, to strictly avoid poppy/poppy seed consumption during study enrolment and the course of the study to avoid positive morphine or morphine glucuronide findings caused by adhering alkaloid residues (from external sources). 1 MESH:D003474 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype bd011e44-bc09-11e5-9b9d-001a4ae51247 10.1016/j.bbadis.2011.09.004 Studies in rodents and humans demonstrated that, after oral administration, curcumin undergoes phase I reactions and is reduced into dihydrocurcumin (DHC), tetrahydrocurcumin (THC), hexahydrocurcumin, octahydrocurcumin and hexahydrocurcuminol as well as phase II reactions originating curcumin glucuronide and curcumin sulfate[22,37,38]. 1 CHEBI:37670 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a799c950-bc3d-11e5-9b9d-001a4ae51247 PMC3516820 Finally, atazanavir, a protease inhibitor affecting glucuronidation, decreases the formation of raltegravir glucuronide and induces a moderate increase in raltegravir concentration [39,47]. 1 MESH:D013467 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype d09821b8-ca01-11e5-b88f-001a4ae51247 15843492 Biosynthesis of Sulindac, Sulindac Sulfone, Indomethacin, Diclofenac, Flurbiprofen, Ketoprofen, and Naproxen Glucuronide Standards.HLMs have been used previously to produce authentic glucuronide standards (Soars et al., 2002). 1 UNIPROT:O75030 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein de285806-ca02-11e5-9b70-001a4ae51247 15980101 "Gemcabene [6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethyl-hexanoic acid (PD0072953)], gemcabene glucuronide [6-[6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethyl-hexanoyloxy]-3,4,5-trihydroxy-tetrahydro-pyran-2-carboxylic acid (PD0329728)], and internal standard [6-(5-carboxy-5-methyl-heptyloxy)-2-ethyl-2-methyl-hexanoic acid (PD0200455)] were all synthesized by the Department of Chemistry, Pfizer Global Research and Development (Ann Arbor, MI;Fig. 1)." 1 MESH:D000077341 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype a1612518-c7cb-11ee-9aaa-0050569a1f61 10.1016/j.pharmthera.2023.108459 Given the apparent predominant roles of P-gp in irinotecan transport, BCRP and P-gp in SN-38 disposition, and BCRP in SN-38 glucuronide efflux (Fig. 5) (Parvez et al., 2021), lapatinib, pazopanib, regorafenib and sorafenib may potentially variably perturb the disposition of SN-38 and SN-38 glucuronide (and the SN-38 to SN-38 glucuronide plasma AUC ratio). 1 UNIPROT:Q9H2S1 decreases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein b9d433b8-bc50-11e5-8abe-001a4ae51246 PMC4030851 The question then is how might inhibition of SK2 and lowering of S1P increase the levels of the glucuronide conjugate of hexadecanol? 1 CHEBI:30089 actelytatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 1a7b7a70-a1fd-11e8-bde0-001a4a160175 PMC6090659 Three acetylated metabolites were present in urine namely, PQ acetate (m/z302.1875) (29), acetylated hydroxyl-PQ glucuronide conjugate (m/z494.2127) (20) andN-Acetyl-PQ quinone-imine (m/z316.1676) (35). 1 CHEBI:16189 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 81dbbdd8-bc54-11e5-8d2d-001a4ae51247 PMC4532713 This can be explained by the slower formation of the glucuronide compared to the sulphate, which causes the recovery of glucuronide in urine to occur later in time.Fig. 1 UNIPROT:O88909 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a200ee56-c9fd-11e5-ab20-001a4ae51246 14762099 "These results suggest that OAT3/Roct accepts sulfate and glucuronide conjugates as a substrate, and is likely to be involved in renal excretion of those conjugates cooperating with OATv1." 1 MESH:D006220 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 44c4aa92-c47c-11e5-9cc6-001a4ae51246 22028316 "In plasma, the concentration of haloperidol glucuronide is highest among the metabolites, followed, in rank order, by unchanged haloperidol, reduced haloperidol, and reduced haloperidol glucuronide (Someya et al., 1992)." 1 CHEBI:12777 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 3bb23c6a-c483-11e5-a92e-001a4ae51246 PMC3261589 Differentiating agents Retinoids, vitamin A derivatives, induce morphologic differentiation of neuroblastoma.51-54 13-cis-retinoic acid (isotretinoin) is a synthetic derivative of the naturally occurring all-trans retinoic acid. 1 MESH:D017239 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 5a0f4224-c8df-11e5-9cb8-001a4ae51247 17135345 "Paclitaxel reduced the systemic elimination of doxorubicinol and increased its plasma levels during the course of doxorubicin-paclitaxel infusions (Gianni et al., 1997); however, paclitaxel increased also the plasma levels of epirubicinol and epirubicinol glucuronide during infusion of the less cardiotoxic paclitaxel-epirubicin combination (Esposito et al., 1999;Grasselli et al., 2001)." 1 UNIPROT:P02774 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 8aab075a-f543-11eb-bcd9-001a4a160176 29481855 GC columns that can be used to up 450° will enable the separation of steroid glucuronide MO-TMS derivatives. 1 UNIPROT:P02774 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 1cf6f17b-f587-11eb-8aac-001a4a160175 30228007 In order to assess the efficiency of the GC derivatisation process, and if this step could cause the release of glucuronide and sulfate moieties prior to analysis by GC–MS, urine samples obtained after processing on both SPE extraction cartridges (Strata SDB-L and Oasis HLB) were derivatized and divided in two aliquots (seeFig. 1 UNIPROT:P29972 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 6856faa4-c464-11e5-9cbe-001a4ae51247 PMC3719771 "The reference standard dolutegravir,15N2H7-dolutegravir stable isotopic label, and dolutegravir glucuronide (GSK2832500; M2) reference standard material were synthesized and supplied by Shionogi and Co., Ltd. (Osaka, Japan)." 1 CHEBI:7625 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical d5c80208-c47e-11e5-8491-001a4ae51247 PMC2888634 Sulindac sulfide (a COX-1 and COX-2 inhibitor), sulindac sulfone (exisulind, a proapoptotic agent that does not inhibit COX), and nordihydroguaiaretic acid (a lipoxygenase inhibitor) each inhibited growth of NSCLC and SCLC cell lines, and were synergistic with paclitaxel, cisplatin, and 13-cis-retinoic acid[426]. 1 MESH:D012293 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 10483c80-c467-11e5-8491-001a4ae51247 24366904 "These studies indicated that rifampicin (a known potent CYP3A4 inducer) moderately increased formation of M2a, M2b, and faldaprevir glucuronide, consistent with the clinical observation of increased faldaprevir clearance by another inducer, efavirenz (Kiser et al., 2013)." 1 CHEBI:39867 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a0eb9ed4-c8e6-11e5-9cb8-001a4ae51247 17409271 "TheN-2 glucuronide is weakly reactive, but the fact that valproic acid inhibits formation of the glucuronide and also increases the risk of idiosyncratic reactions argues against this metabolite as the cause of adverse reactions (Yuen et al., 1992)." 1 MESH:D007052 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 Thus, liver metabolism of a high dose of ibuprofen may produce ibuprofen-acyl glucuronide levels such as to guarantee a local concentration sufficient for inhibiting TRPA1. 1 MESH:D007052 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype e61651da-c47b-11e5-85e4-001a4ae51246 PMC3101013 "6B, ibuprofen was metabolized to produce ibuprofen glucuronide, 1-OH-ibuprofen, 2-OH-ibuprofen, and carboxyl-ibuprofen in mouse plasma; this metabolic profile was the same as that after PI administration." 1 MESH:D007052 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 25ea117e-f58b-11eb-8c11-001a4a160175 30794923 Our findings add new insights into the antinociceptive/anti-hyperalgesic and anti-inflammatory activity of ibuprofen which, in addition to COX inhibition, attenuates TRPA1 activityviaibuprofen-acyl glucuronide generation. 1 MESH:D002117 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype cf268898-c8e8-11e5-a1fd-001a4ae51246 18281521 "These results show that calcitriol inhibits the glucuronide conjugation of DHT and its 5α-reduced metabolites 3α-diol and ADT in LNCaP cells." 1 UNIPROT:Q40190 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein c979c2fe-c9fe-11e5-ab20-001a4ae51246 14744948 "The instability of M-7 necessitated the structural analysis of a synthetic glucuronide containing protecting groups to stabilize the molecule." 1 MESH:D004202 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 005133a8-352c-11e8-a34b-001a4a160175 27341547 As a result, it has been proven that disinfectant abuse caused the excessive excretion of 2-propyl glucuronide in the urine of our acutely intoxicated and chronically alcohol-dependent patient with a history of industrial cleaning fluid abuse. 1 UNIPROT:O60656 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a2df9c38-c466-11e5-91a7-001a4ae51247 PMC3837878 "DHA, in turn, undergoes glucuronide conjugation mediated by UGT2B7 and UGT1A9." 1 UNIPROT:O60656 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein a57febc2-c47b-11e5-9cc6-001a4ae51246 21673130 "From the tested UGTs, only UGT1A9, UGT1A4, UGT2B7, UGT2B4, and UGT2B17 produced significant amounts of eslicarbazepine glucuronide." 1 UNIPROT:O60656 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 8fcb860a-ae95-11ec-840e-0050569a791b PMCPMC8504117 With a β-OH on the anthraquinone ring, emodin acquired high glucuronidation activities and primarily transformed into emodin glucuronide with exceedingly low absorption and bioavailability, catalyzed by UDP-glucuronosyltransferases (UGTs) 1A1 and UGT1A9 [198, 199]. 1 UNIPROT:O60656 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 52010550-c718-11ee-b346-0050569a791b 10.1016/j.lfs.2023.122119 Etoposide and some of its derivates are also inactivated by glutathione and glucuronide conjugations mediated by glutathione S-transferase (GST) and UGT1 enzymes, respectively [72]. 1 UNIPROT:O60656 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 94d0dfda-351b-11e8-a34b-001a4a160175 28246004 Contribution of UGTs to the glucuronidation of genistein in liver and kidney A panel of recombinant human UGTs was used to screen for the glucuronidation of genistein using our previous published data[21], which proved that UGT1A1, UGT1A8, UGT1A9, and UGT1A10 produced a significant amount of glucuronide metabolite (Fig. 2A). 1 UNIPROT:O60656 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 884bcba4-c8ed-11e5-9faa-001a4ae51247 PMC2615638 "The formation of MG5, the most abundant isoliquiritigenin glucuronide, was catalyzed by several UGTs but predominantly by UGT1A1 and UGT1A9 (Fig. 5)." 1 CHEBI:71219 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a1612518-c7cb-11ee-9aaa-0050569a1f61 10.1016/j.pharmthera.2023.108459 Given the apparent predominant roles of P-gp in irinotecan transport, BCRP and P-gp in SN-38 disposition, and BCRP in SN-38 glucuronide efflux (Fig. 5) (Parvez et al., 2021), lapatinib, pazopanib, regorafenib and sorafenib may potentially variably perturb the disposition of SN-38 and SN-38 glucuronide (and the SN-38 to SN-38 glucuronide plasma AUC ratio). 1 MESH:D013693 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 1ebec12c-c47a-11e5-85e4-001a4ae51246 21245208 "Temazepam is eliminated mainly by conjugation, yielding temazepam glucuronide; to a lesser extent, it is demethylated to oxazepam (Fig. 6A), which is further conjugated to oxazepam glucuronide (Locniskar and Greenblatt, 1990)." 1 CHEBI:29309 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 4ca99d60-bbd7-11e5-956b-001a4ae51247 10.1016/j.steroids.2008.11.012 Methyl (androsta-1,4-dien-17α-ol-3-one)-17β-O-2,3,4-tri-O-acetyl-β-d-glucuronate (4a) Synthesis of the glucuronide donor: methyl-(2,3,4-tri-O-acetyl-α-d-glucopyranosyl-trichloroacetimidate)-glucuronate (7) H2O (50μl) and acetobromo-α-d-glucuronic acid methyl ester (5) (1.5mmol, 600mg) were added in sequence to a suspension of CdCO3(1.5mmol, 500mg) in acetonitrile. 1 UNIPROT:P33527 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 8fa71ec6-bc4a-11e5-8abe-001a4ae51246 10.1016/j.ejphar.2008.06.079 Physiologically, ABCC1 contributes to Phase II metabolism by transporting a range of glutathione, glucuronide and sulfate conjugates (Keppler et al., 1997), and limits the toxicity of such metabolites in the central nervous system and other sanctuary tissue sites (Wijnholds et al., 2000; Wijnholds et al., 1998). 1 UNIPROT:P33527 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein f5c96be0-aa75-11e6-bcbe-001a4ae51246 PMC5129306 Multidrug resistance-associated protein 1 (MRP1/ABCC1) mediated the active efflux of glucuronide, glutathione, and sulfate conjugates [42]. 1 UNIPROT:P33527 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 71ed5092-c8e5-11e5-9ad8-001a4ae51247 17264072 ABCC1 has been demonstrated to mediate ATP-dependent cellular efflux of a wide variety of anticancer drugs and xenobiotics and a broad spectrum of organic anions, including GSSG and GSH as well as anionic conjugates of GSH, glucuronide, and sulfate (3,5). 1 PF:PF06816 increases 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 ProteinFamily bf22bc94-c480-11e5-85e4-001a4ae51246 PMC2974608 Using serum from these patients, we tested whether the NOD/scid mouse, when challenged with naproxen or acetaminophen, would produce a sufficient amount of the glucuronide conjugate to promote platelet clearance by the metabolite-specific antibodies. 1 MESH:D000082 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype e3a635bc-c47d-11e5-91a7-001a4ae51247 PMC3043622 One gram of acetaminophen was given at ∼0630 and repeated at ∼0845 to enable measurement of urinary glucuronide. 1 MESH:D000082 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c9de5be8-c467-11e5-8491-001a4ae51247 PMC3891223 At ∼0630, 1 g of acetaminophen was given and repeated at ∼0845 to enable measurement of urinary glucuronide. 1 MESH:D000082 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 75b08d06-3905-11e8-bf76-001a4a160175 PMC5616013 Briefly, hepatic metabolism of APAP by phase II conjugation produces nontoxic glucuronide and sulphate metabolites. 1 PUBCHEM:50599 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 03adc30a-c467-11e5-85e4-001a4ae51246 24346835 "Gemfibrozil glucuronide further highlights the need for more consistent characterization of the DDI potential of glucuronide metabolites in a prospective manner to avoid empirical DDI discovery in clinical practice." 1 CHEBI:72544 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical ef48bd52-c484-11e5-a92e-001a4ae51246 22649189 Kinetics for inhibition of SULT-catalyzed conversion of 7HC into 7HCS and of oxidation and glucuronidation of 1ʹ-hydroxyestragole into 1ʹ-oxoestragole and 1ʹ-hydroxyestragole glucuronide by selected flavonoids. 1 CHEBI:72544 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 95d71542-c9bd-11ee-8b99-0050569a1f61 10.1016/j.jff.2022.105352 Flavonoids and procyanidins found on avocado seeds extract are able to inhibit NADPH oxidase activity (3′-O-methyl epicatechin, procyanidin B2, (-)-epicatechin glucuronide and vanillic acid) (Steffen et al., 2008), activation and regulation of the transcription factor NF-кB by different mechanisms (epigallocatechin gallate, epigallocatechin and procyanidin trimer), and the constitutive activation of mitogen-activated protein kinase (MAPK proteins) (Terra et al., 2007, 2011). 1 MESH:D047310 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype 207c2688-bc4d-11e5-8d2d-001a4ae51247 PMC3414224 Due to the absorption and disposition of flavonoids being similar to that of RLX in enterocytes, apigenin competitively inhibited the formation of RLX glucuronide and RLX sulfate in the gut; therefore, apigenin could improve the absorption fraction of intact RLX from intestine during transport across mono-layer enterocyte.13Metabolic inhibition and kinetic RLX by bioactive excipients have been investigated by Kim et al.14Their study aimed at modulating poorly bioavailable drugs via decreasing the first-pass metabolism in gastrointestinal tract and liver and inhibition of P-gp efflux transporters. 1 MESH:D047311 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Phenotype c204abae-caf1-11ee-b346-0050569a791b 10.1016/j.lwt.2015.11.017 The proposed candidate for peakC43was luteolin-3-O-glucuronide, which presented molecular ion atm/z461 and produced the predominant fragment atm/z285 corresponding to deprotonated luteolin (loss of glucuronide molecule withm/z176). 1 UNIPROT:Q9UNQ0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 39e8bc00-c8e9-11e5-9624-001a4ae51246 18474677 "Because Zamek-Gliszczynski et al. (2006b) reported that Bcrp mediates biliary excretion of some glucuronide conjugates together with Mrp2 in mice, Bcrp is one of the candidate transporters." 1 UNIPROT:Q9UNQ0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein bf033980-ca5e-11e5-9088-001a4ae51247 12874005 The determination that ABCG2 is also able to mediate the transport of the glucuronide E217βG, together with a previous report indicating that it is also able to transport SN38-glucuronide(42), indicates that the substrate selectivity of the pump is unexpectedly broad with regard to amphipathic anions. 1 UNIPROT:Q9UNQ0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 61591280-aa7f-11e6-bcbe-001a4ae51246 PMC5104480 In addition, this work established that BCRP-mediated excretion was the predominant pathway for diosmetin and chrysoeriol disposition, which could help increase the understanding and prediction of BCRP-mediated glucuronide CLin vivo. 1 UNIPROT:Q9UNQ0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 1f2e431e-351e-11e8-8f56-001a4a160175 PMC5613675 In this cell model, the kinetic parameters of BCRP-mediated glucuronide efflux were determined by the measurement of intracellular glucuronide concentrations and the corresponding excretion rates of glucuronides [56]. 1 UNIPROT:Q9UNQ0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 9a650e98-c8e5-11e5-a1fd-001a4ae51246 17470645 "For the efflux transport of glucuronide conjugates in the luminal side, MRP2 and BCRP have been shown to mediate the intestinal efflux of the glucuronide conjugates of xenobiotics (Adachi et al., 2005)." 1 UNIPROT:Q9UNQ0 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 1bd8f42c-375b-11e8-8636-001a4a160175 20227439 Urinary efflux of sulfated hormones will most likely be mediated by BCRP in the apical membrane, whereas MRP2 and MRP4 can transport the glucuronide conjugates (Imai et al., 2003; Deeley et al., 2006; Huls et al., 2008). 1 UNIPROT:P21128 hydroxylatesProtein 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 770ff3aa-c674-11ee-b346-0050569a791b 10.1016/j.jep.2023.117360 By comparing the brain components of healthy rats and model rats, we found that the different components were isoliquiritigenin (P11), liquiritin apioside (P13), senkyunolide D (P21), genkwanin (P34), etc. Apigenin-O-sulphate glucuronide (M11), hydroxylated 3-butylidenephthalide glucuronide (M30), oxidated ligustilide (M32), hydrated senkyunolide A (M37), oxidated senkyunolide A (M39), hydroxylated 3-butylidenephthalide (M42) and senkyunolide J acetycysteine (M43), which existed only in the whole brain of model rats. 1 UNIPROT:P09875 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein b6ba82ba-ca5e-11e5-8050-001a4ae51246 12867487 "A glucuronide conjugate of nonylphenol was produced by UGT2B1 (Fig. 1D), indicating that the main metabolite in the liver perfusion is NP-G." 1 CHEBI:16234 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical e2bb3afa-aaa1-11e8-89c7-001a4a160175 PMC6225321 In explanation, aromatic hydroxy groups are almost invariably metabolized in phase II to the highly water-soluble and rapidly eliminated glucuronide (and sometimes sulfate) conjugates. 1 CHEBI:16234 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 2373a080-3916-11e8-87fd-001a4a160176 24076267 The major metabolic step is glucuronidation at the phenolic hydroxyl group, which produces mycophenolic acid glucuronide, an inactive metabolite (Bullingham et al., 1998). 1 CHEBI:16234 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical f4807834-cc75-11e5-b6ad-001a4ae51246 9353359 "In addition, the presence of the hydroxyl group on the ring enhances glucuronide or sulfate conjugation, resulting in the formation of an inactive compound that is readily excreted (Kruseet al., 1987)." 1 CHEBI:16234 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 7ccaa7bc-bc38-11e5-8d2d-001a4ae51247 PMC3307704 The methoxy substitution for these hydroxyl groups on our lead compound2should prevent these glucuronide and sulfate additions and contribute to sustained bioactivity. 1 CHEBI:421707 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical 749cc17c-c9ff-11e5-ab20-001a4ae51246 15205392 Members of the ABC family of MRPs, such as MRP1, MRP2, and MRP3, accept glucuronide conjugates. 1 CHEBI:68647 inhibits 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Chemical a1612518-c7cb-11ee-9aaa-0050569a1f61 10.1016/j.pharmthera.2023.108459 Given the apparent predominant roles of P-gp in irinotecan transport, BCRP and P-gp in SN-38 disposition, and BCRP in SN-38 glucuronide efflux (Fig. 5) (Parvez et al., 2021), lapatinib, pazopanib, regorafenib and sorafenib may potentially variably perturb the disposition of SN-38 and SN-38 glucuronide (and the SN-38 to SN-38 glucuronide plasma AUC ratio). 1 UNIPROT:P0ACT6 activates 1-O-all-trans-retinoyl-beta-glucuronic acid CHEBI:28870 Protein 2d4433f0-354f-11e9-913f-001a4a160175 PMC5777068 Discussion The structural basis of GusR-mediated glucuronide recognition by members of the human gut Enterobacteriaceae pathobiontsE.