General Information of Drug-Metabolizing Enzyme (DME) (ID: DE85D2P)

DME Name UDP-glucuronosyltransferase 1A9 (UGT1A9)
Synonyms UDP-glucuronosyltransferase family 1 member A9; UDP-glucuronosyltransferase 1-I; UDP-glucuronosyltransferase 1-9; UDPGT 1-9; UGT-1I; UGT1*9; UGT1-09; UGT1.9; UGT1A9; UGT1I; lugP4
Gene Name UGT1A9
UniProt ID
UD19_HUMAN
INTEDE ID
DME0042
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
54600
EC Number EC: 2.4.1.17
Transferase
Glycosyltransferases
Hexosyltransferase
EC: 2.4.1.17
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MACTGWTSPLPLCVCLLLTCGFAEAGKLLVVPMDGSHWFTMRSVVEKLILRGHEVVVVMP
EVSWQLGRSLNCTVKTYSTSYTLEDLDREFKAFAHAQWKAQVRSIYSLLMGSYNDIFDLF
FSNCRSLFKDKKLVEYLKESSFDAVFLDPFDNCGLIVAKYFSLPSVVFARGILCHYLEEG
AQCPAPLSYVPRILLGFSDAMTFKERVRNHIMHLEEHLLCHRFFKNALEIASEILQTPVT
EYDLYSHTSIWLLRTDFVLDYPKPVMPNMIFIGGINCHQGKPLPMEFEAYINASGEHGIV
VFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGH
PMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDL
ENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTW
YQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Function This enzyme has specificity for phenols.
KEGG Pathway
Ascorbate and aldarate metabolism (hsa00053 )
Chemical carcinogenesis (hsa05204 )
Drug metabolism - cytochrome P450 (hsa00982 )
Drug metabolism - other enzymes (hsa00983 )
Metabolic pathways (hsa01100 )
Metabolism of xenobiotics by cytochrome P450 (hsa00980 )
Pentose and glucuronate interconversions (hsa00040 )
Porphyrin and chlorophyll metabolism (hsa00860 )
Retinol metabolism (hsa00830 )
Steroid hormone biosynthesis (hsa00140 )
Reactome Pathway
PPARA activates gene expression (R-HSA-1989781 )
Glucuronidation (R-HSA-156588 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
38 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [1]
Ambrisentan DMD1QXW Pulmonary arterial hypertension BB01.0 Approved [2]
Canagliflozin DMFRM1I Non-insulin dependent diabetes 5A11 Approved [3]
Dapagliflozin DM28UJG Non-insulin dependent diabetes 5A11 Approved [4]
Darolutamide DMV7YFT Prostate cancer 2C82.0 Approved [5]
Dexibuprofen DMFYBD0 Ankylosing spondylitis FA92.0 Approved [6]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [7]
Dihydroartemisinin DMBXVMZ Malaria 1F40-1F45 Approved [8]
Empagliflozin DMRF9YK Type-1 diabetes 5A10 Approved [9]
Entacapone DMLBVKQ Parkinson disease 8A00.0 Approved [10]
Etodolac DM6WJO9 Osteoarthritis FA00-FA05 Approved [6]
Fenofibrate DMFKXDY Coronary atherosclerosis Approved [11]
Flurbiprofen DMGN4BY Osteoarthritis FA00-FA05 Approved [6]
Fostamatinib DM6AUHV Immune thrombocytopenic purpura 3B64.13 Approved []
Gemfibrozil DMD8Q3J Hyperlipidaemia 5C80 Approved [12]
Haloperidol DM96SE0 Delirium Approved [6]
Ibuprofen DM8VCBE Dysmenorrhea GA34.3 Approved [6]
Indomethacin DMSC4A7 Bursitis Approved [13]
Ketobemidone DMM3L6Z Pain MG30-MG3Z Approved [6]
Labetalol DMK8U72 Hypertension BA00-BA04 Approved [14]
Lumiracoxib DM1S4AG Chronic renal failure GB61.Z Approved [6]
Mycophenolate mofetil DMPQAGE Hepatosplenic T-cell lymphoma Approved [15]
Mycophenolic acid DMRBMAU Crohn disease DD70 Approved [16]
Naproxen DMZ5RGV Bursitis Approved [17]
Nateglinide DMLK2QH Diabetic complication 5A2Y Approved [6]
PF-04449913 DMSB068 Chronic myelomonocytic leukaemia 2A40 Approved [18]
PF-04971729 DM79VXT Type-2 diabetes 5A11 Approved [19]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [6]
Regorafenib DMHSY1I Gastrointestinal stromal tumour 2B5B Approved [20]
Retigabine DMGNYIH Behcet disease 4A62 Approved [21]
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [22]
Sulfamethoxazole DMB08GE Acute otitis media AB00 Approved [6]
Tapentadol hydrochloride DMXLSH3 Acute pain MG31 Approved [23]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [24]
Valdecoxib DMAY7H4 Osteoarthritis FA00-FA05 Approved [6]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [6]
Vorinostat DMWMPD4 Adult acute monocytic leukemia Approved [25]
Zileuton DMVRIC2 Allergic asthma CA23.0 Approved [6]
⏷ Show the Full List of 38 Approved Drug(s)
10 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ataluren DM4GXW3 Cystic fibrosis CA25 Phase 3 [26]
Curcumin DMQPH29 Solid tumour/cancer 2A00-2F9Z Phase 3 [27]
Dabigatran etexilate DMRDZ4X Venous thromboembolism BD72 Phase 3 [28]
GSK1265744 DMT8J0I Human immunodeficiency virus infection 1C62 Phase 3 [29]
MURAGLITAZAR DMG3NFZ N. A. N. A. Phase 3 [30]
BCP-13498 DM2BO9W N. A. N. A. Phase 2 [1]
LE-SN38 DMW50NF Colorectal cancer 2B91.Z Phase 2 [31]
Topiroxostat DMA04DE Gout FA25 Phase 2 [32]
Vadimezan DMK7CYX Solid tumour/cancer 2A00-2F9Z Phase 2 [33]
LM-94 DMW3QGJ N. A. N. A. Phase 1/2 [34]
⏷ Show the Full List of 10 Clinical Trial Drug(s)
1 Patented Agent(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
EUGENOL DM7US1H Discovery agent N.A. Patented [27]
2 Discontinued Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Seratrodast DMPNTDL Allergic asthma CA23.0 Discontinued in Phase 3 [6]
Gavestinel DM8IL1U Nerve injury ND56.4 Discontinued in Phase 2 [6]
3 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Anthraflavic acid DMN1YFU N. A. N. A. Investigative [27]
Chrysin DM7V2LG Discovery agent N.A. Investigative [27]
phloretin DMYA50U Discovery agent N.A. Investigative [27]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
Chrysin Discovery agent [N.A.] Investigative Km = 0.004 microM [27]
phloretin Discovery agent [N.A.] Investigative Km = 0.0068 microM [27]
EUGENOL Discovery agent [N.A.] Patented Km = 0.0084 microM [27]
Curcumin Solid tumour/cancer [2A00-2F9Z] Phase 3 Km = 0.1 microM [27]
Propofol Anaesthesia [9A78.6] Approved Km = 0.0072 microM [34]

References

1 Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
2 Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805.
3 Effects of rifampin, cyclosporine A, and probenecid on the pharmacokinetic profile of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants. Int J Clin Pharmacol Ther. 2015 Feb;53(2):115-28.
4 Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27.
5 Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):747-759.
6 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
7 Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
8 Eurartesim - European Medicines Agency
9 Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.
10 Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos. 2005 Jul;33(7):1017-26.
11 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
12 The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4.
13 Contribution of UDP-glucuronosyltransferases 1A9 and 2B7 to the glucuronidation of indomethacin in the human liver. Eur J Clin Pharmacol. 2007 Mar;63(3):289-96.
14 Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination. Xenobiotica. 2008 Jan;38(1):62-75.
15 The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
16 Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite. Drug Metab Dispos. 2011 Mar;39(3):448-55.
17 S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. Br J Clin Pharmacol. 2005 Oct;60(4):423-33.
18 Metabolism, excretion and pharmacokinetics of [14C]glasdegib (PF-04449913) in healthy volunteers following oral administration. Xenobiotica. 2017 Dec;47(12):1064-1076.
19 The effect of renal impairment on the pharmacokinetics and pharmacodynamics of ertugliflozin in subjects with type 2 diabetes mellitus. J Clin Pharmacol. 2017 Nov;57(11):1432-1443.
20 FDA Label of Regorafenib. The 2020 official website of the U.S. Food and Drug Administration.
21 Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12.
22 Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
23 Investigations into the drug-drug interaction potential of tapentadol in human liver microsomes and fresh human hepatocytes. Drug Metab Lett. 2008 Jan;2(1):67-75.
24 The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.
25 Age-dependent hepatic UDP-glucuronosyltransferase gene expression and activity in children. Front Pharmacol. 2016 Nov 16;7:437.
26 Ataluren pharmacokinetics in healthy Japanese and Caucasian subjects. Clin Pharmacol Drug Dev. 2019 Feb;8(2):172-178.
27 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.
28 Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75.
29 Disposition and metabolism of cabotegravir: a comparison of biotransformation and excretion between different species and routes of administration in humans. Xenobiotica. 2016;46(2):147-62.
30 Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar. Drug Metab Dispos. 2007 Jan;35(1):139-49.
31 Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene. Oncol Lett. 2012 Mar;3(3):694-698.
32 Characterization of N-glucuronidation of 4-(5-pyridin-4-yl-1H-[1,2,4]triazol-3-yl) pyridine-2-carbonitrile (FYX-051): a new xanthine oxidoreductase inhibitor. Drug Metab Dispos. 2007 Dec;35(12):2143-8.
33 Predicting pharmacokinetics and drug interactions in patients from in vitro and in vivo models: the experience with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an anti-cancer drug eliminated mainly by conjugation. Drug Metab Rev. 2002 Nov;34(4):751-90.
34 The "albumin effect" and drug glucuronidation: bovine serum albumin and fatty acid-free human serum albumin enhance the glucuronidation of UDP-glucuronosyltransferase (UGT) 1A9 substrates but not UGT1A1 and UGT1A6 activities. Drug Metab Dispos. 2008 Jun;36(6):1056-62.