Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4JJ32)

• DOT Name: UDP-glucuronosyltransferase 1A7
• Synonyms: UGT1A7; EC 2.4.1.17; UDP-glucuronosyltransferase 1-7; UDPGT 1-7; UGT1*7; UGT1-07; UGT1.7; UDP-glucuronosyltransferase 1-G; UGT-1G; UGT1G
• Gene Name: UGT1A7
• UniProt ID: UD17_HUMAN
• EC Number: 2.4.1.17
• Pfam ID: PF00201
• Sequence:
  MARAGWTGLLPLYVCLLLTCGFAKAGKLLVVPMDGSHWFTMQSVVEKLILRGHEVVVVMP
  EVSWQLGRSLNCTVKTYSTSYTLEDQDREFMVFADARWTAPLRSAFSLLTSSSNGIFDLF
  FSNCRSLFNDRKLVEYLKESCFDAVFLDPFDACGLIVAKYFSLPSVVFARGIFCHYLEEG
  AQCPAPLSYVPRLLLGFSDAMTFKERVWNHIMHLEEHLFCPYFFKNVLEIASEILQTPVT
  AYDLYSHTSIWLLRTDFVLEYPKPVMPNMIFIGGINCHQGKPVPMEFEAYINASGEHGIV
  VFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGH
  PMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDL
  ENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTW
  YQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
• Function: [Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of endogenous estrogen hormone epiestradiol. Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties. Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II. Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan. Also metabolizes mycophenolate, an immunosuppressive agent ; [Isoform 2]: Lacks UGT glucuronidation activity but acts as a negative regulator of isoform 1.
• Tissue Specificity: Liver and gastric tissue . Isoform 1 and isoform 2 are expressed in esophagus. Neither isoform is expressed in liver, kidney, colon and small intestine .
• KEGG Pathway:
  Pentose and glucuro.te interconversions (hsa00040)
  Ascorbate and aldarate metabolism (hsa00053)
  Steroid hormone biosynthesis (hsa00140)
  Retinol metabolism (hsa00830)
  Porphyrin metabolism (hsa00860)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
  Bile secretion (hsa04976)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  Aspirin ADME (R-HSA-9749641)
  Glucuronidation (R-HSA-156588)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 50 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Acetaminophen.	[15]
Estradiol	DMUNTE3	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Estradiol.	[15]
Aspirin	DM672AH	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Aspirin.	[15]
Irinotecan	DMP6SC2	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Irinotecan.	[16]
Diclofenac	DMPIHLS	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Diclofenac.	[15]
Indomethacin	DMSC4A7	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Indomethacin.	[15]
Capsaicin	DMGMF6V	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Capsaicin.	[17]
Ibuprofen	DM8VCBE	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Ibuprofen.	[15]
Estrone	DM5T6US	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Estrone.	[15]
Estriol	DMOEM2I	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Estriol.	[15]
Masoprocol	DMMVNZ0	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Masoprocol.	[17]
Flurbiprofen	DMGN4BY	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Flurbiprofen.	[15]
Mefenamic acid	DMK7HFI	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Mefenamic acid.	[15]
Salicyclic acid	DM2F8XZ	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Salicyclic acid.	[15]
Furosemide	DMMQ8ZG	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Furosemide.	[15]
Entacapone	DMLBVKQ	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Entacapone.	[18]
Ofloxacin	DM0VQN3	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Ofloxacin.	[19]
Fenoprofen	DML5VQ0	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Fenoprofen.	[15]
Diflunisal	DM7EN8I	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Diflunisal.	[15]
Felbinac	DMKZEIB	Approved	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Felbinac.	[15]
Resveratrol	DM3RWXL	Phase 3	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Resveratrol.	[20]
Curcumin	DMQPH29	Phase 3	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Curcumin.	[17]
Genistein	DM0JETC	Phase 2/3	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Genistein.	[17]
Sitafloxacin	DMTV5XC	Phase 2	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Sitafloxacin.	[19]
Eugenol	DM7US1H	Patented	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Eugenol.	[17]
T83193	DMHO29Y	Patented	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of T83193.	[15]
Steroid derivative 1	DMB0NVQ	Patented	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Steroid derivative 1.	[15]
Ferulic Acid	DMJC7NF	Patented	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Ferulic Acid.	[15]
INDOPROFEN	DM5QSKN	Withdrawn from market	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of INDOPROFEN.	[15]
EMODIN	DMAEDQG	Terminated	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of EMODIN.	[17]
Coumestrol	DM40TBU	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Coumestrol.	[17]
Chrysin	DM7V2LG	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Chrysin.	[17]
Daidzein	DMRFTJX	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Daidzein.	[17]
Apigenin	DMI3491	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Apigenin.	[17]
biochanin A	DM0HPWY	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of biochanin A.	[17]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of 3,7,3',4'-TETRAHYDROXYFLAVONE.	[17]
methyl salicylate	DMKCG8H	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of methyl salicylate.	[15]
Plumbagin	DM9BS50	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Plumbagin.	[17]
Formononetin	DM7WFZ8	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Formononetin.	[17]
Mononitrophenol	DM4QO9G	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Mononitrophenol.	[18]
2-hydroxy-17beta-estradiol	DMM9Z0B	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of 2-hydroxy-17beta-estradiol.	[15]
Fibrates	DMFNTMY	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Fibrates.	[15]
Cinnamic acid	DM340FH	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Cinnamic acid.	[15]
ACMC-1AKLT	DMRQ70X	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of ACMC-1AKLT.	[22]
Hydroxyestrone	DMBO7ZD	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Hydroxyestrone.	[15]
BRN-1999480	DMC9Q4D	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of BRN-1999480.	[15]
Anthraflavic acid	DMN1YFU	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Anthraflavic acid.	[17]
SCOPOLETIN	DM645FP	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of SCOPOLETIN.	[18]
Quinizarin	DMRQCK3	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Quinizarin.	[17]
Diphenylacetic Acid	DMP6IHR	Investigative	UDP-glucuronosyltransferase 1A7 increases the glucuronidation of Diphenylacetic Acid.	[15]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Puerarin	DMJIMXH	Phase 2	UDP-glucuronosyltransferase 1A7 increases the metabolism of Puerarin.	[21]

23 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the activity of UDP-glucuronosyltransferase 1A7.	[1]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of UDP-glucuronosyltransferase 1A7.	[2]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of UDP-glucuronosyltransferase 1A7.	[3]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of UDP-glucuronosyltransferase 1A7.	[4]
Osimertinib	DMRJLAT	Approved	Osimertinib decreases the activity of UDP-glucuronosyltransferase 1A7.	[5]
Tucatinib	DMBESUA	Approved	Tucatinib decreases the activity of UDP-glucuronosyltransferase 1A7.	[6]
Opicapone	DM1BKA6	Approved	Opicapone decreases the activity of UDP-glucuronosyltransferase 1A7.	[7]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of UDP-glucuronosyltransferase 1A7.	[8]
LM-94	DMW3QGJ	Phase 1/2	LM-94 increases the activity of UDP-glucuronosyltransferase 1A7.	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of UDP-glucuronosyltransferase 1A7.	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of UDP-glucuronosyltransferase 1A7.	[11]
Kaempferol	DMHEMUB	Investigative	Kaempferol decreases the activity of UDP-glucuronosyltransferase 1A7.	[1]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the activity of UDP-glucuronosyltransferase 1A7.	[8]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the activity of UDP-glucuronosyltransferase 1A7.	[1]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the activity of UDP-glucuronosyltransferase 1A7.	[8]
Morin	DM2OGZ5	Investigative	Morin decreases the activity of UDP-glucuronosyltransferase 1A7.	[1]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the activity of UDP-glucuronosyltransferase 1A7.	[12]
Galangin	DM5TQ2O	Investigative	Galangin decreases the activity of UDP-glucuronosyltransferase 1A7.	[1]
P-Coumaric Acid	DMGJSVD	Investigative	P-Coumaric Acid decreases the activity of UDP-glucuronosyltransferase 1A7.	[8]
Phloretin	DMYA50U	Investigative	Phloretin decreases the activity of UDP-glucuronosyltransferase 1A7.	[8]
AMENTOFLAVONE	DMLRNV2	Investigative	AMENTOFLAVONE decreases the activity of UDP-glucuronosyltransferase 1A7.	[13]
pregnenolone-16alpha-carbonitrile	DM0LW7G	Investigative	pregnenolone-16alpha-carbonitrile increases the expression of UDP-glucuronosyltransferase 1A7.	[14]
Phlorizin	DMNARGO	Investigative	Phlorizin decreases the activity of UDP-glucuronosyltransferase 1A7.	[8]

References

• [1] Potential interactions among myricetin and dietary flavonols through the inhibition of human UDP-glucuronosyltransferase in vitro. Toxicol Lett. 2022 Apr 1;358:40-47. doi: 10.1016/j.toxlet.2022.01.007. Epub 2022 Jan 19.
• [2] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [3] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [4] Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):86-96.
• [5] In vitro inhibition of human UDP-glucuronosyltransferase (UGT) 1A1 by osimertinib, and prediction of in vivo drug-drug interactions. Toxicol Lett. 2021 Sep 15;348:10-17. doi: 10.1016/j.toxlet.2021.05.004. Epub 2021 May 24.
• [6] Drug-drug interaction potentials of tucatinib inhibition of human UDP-glucuronosyltransferases. Chem Biol Interact. 2023 Aug 25;381:110574. doi: 10.1016/j.cbi.2023.110574. Epub 2023 May 30.
• [7] In vitro effects of opicapone on activity of human UDP-glucuronosyltransferases isoforms. Toxicol Lett. 2022 Aug 15;367:3-8. doi: 10.1016/j.toxlet.2022.07.003. Epub 2022 Jul 8.
• [8] Phloretin exhibits potential food-drug interactions by inhibiting human UDP-glucuronosyltransferases in vitro. Toxicol In Vitro. 2022 Oct;84:105447. doi: 10.1016/j.tiv.2022.105447. Epub 2022 Jul 19.
• [9] Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases. Food Chem Toxicol. 2016 Apr;90:112-22.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Piceatannol exhibits potential food-drug interactions through the inhibition of human UDP-glucuronosyltransferase (UGT) in Vitro. Toxicol In Vitro. 2020 Sep;67:104890. doi: 10.1016/j.tiv.2020.104890. Epub 2020 May 22.
• [13] Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases. Chem Biol Interact. 2018 Mar 25;284:48-55.
• [14] Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem. 2005 Nov 11;280(45):37547-57.
• [15] Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
• [16] Identification and characterization of a functional TATA box polymorphism of the UDP glucuronosyltransferase 1A7 gene. Mol Pharmacol. 2005 May;67(5):1732-9.
• [17] Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake. J Biol Chem. 2004 Jan 9;279(2):1429-41.
• [18] Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos. 2005 Jul;33(7):1017-26.
• [19] Acyl glucuronidation of fluoroquinolone antibiotics by the UDP-glucuronosyltransferase 1A subfamily in human liver microsomes. Drug Metab Dispos. 2005 Jun;33(6):803-11. doi: 10.1124/dmd.104.003178. Epub 2005 Mar 15.
• [20] Differences in the glucuronidation of resveratrol and pterostilbene: altered enzyme specificity and potential gender differences. Drug Metab Pharmacokinet. 2014;29(2):112-9. doi: 10.2133/dmpk.dmpk-13-rg-012. Epub 2013 Aug 20.
• [21] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for puerarin metabolism in human liver microsomes. Arch Toxicol. 2012 Nov;86(11):1681-90. doi: 10.1007/s00204-012-0874-7. Epub 2012 May 31.
• [22] Phase II metabolism of betulin by rat and human UDP-glucuronosyltransferases and sulfotransferases. Chem Biol Interact. 2019 Apr 1;302:190-195. doi: 10.1016/j.cbi.2019.02.009. Epub 2019 Feb 15.