Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE2GB8N)

• DME Name: UDP-glucuronosyltransferase 1A8 (UGT1A8)
• Synonyms: UDP-glucuronosyltransferase family 1 member A8; UDP-glucuronosyltransferase 1-H; UDP-glucuronosyltransferase 1-8; UDPGT 1-8; UGT-1H; UGT1*8; UGT1-08; UGT1.8; UGT1A8; UGT1H
• Gene Name: UGT1A8
• UniProt ID: UD18_HUMAN
• INTEDE ID: DME0064
• Gene ID: 54576
• 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:
  MARTGWTSPIPLCVSLLLTCGFAEAGKLLVVPMDGSHWFTMQSVVEKLILRGHEVVVVMP
  EVSWQLGKSLNCTVKTYSTSYTLEDLDREFMDFADAQWKAQVRSLFSLFLSSSNGFFNLF
  FSHCRSLFNDRKLVEYLKESSFDAVFLDPFDACGLIVAKYFSLPSVVFARGIACHYLEEG
  AQCPAPLSYVPRILLGFSDAMTFKERVRNHIMHLEEHLFCQYFSKNALEIASEILQTPVT
  AYDLYSHTSIWLLRTDFVLDYPKPVMPNMIFIGGINCHQGKPLPMEFEAYINASGEHGIV
  VFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGH
  PMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDL
  ENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTW
  YQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
• Function: This enzyme is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
• 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: Glucuronidation (R-HSA-156588)

Molecular Interaction Atlas (MIA) of This DME

3 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Darolutamide	DMV7YFT	Prostate cancer	2C82.0	Approved	[1]
Empagliflozin	DMRF9YK	Type-1 diabetes	5A10	Approved	[2]
Vorinostat	DMWMPD4	Cutaneous T-cell lymphoma	2B01	Approved	[3]

2 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[4]
Afimoxifene	DMFORDT	Breast cancer	2C60-2C65	Phase 2	[5]

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	[4]

4 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anthraflavic acid	DMN1YFU	Discovery agent	N.A.	Investigative	[4]
Chrysin	DM7V2LG	Discovery agent	N.A.	Investigative	[4]
Cis-4-hydroxytamoxifen	DMRFTB5	Discovery agent	N.A.	Investigative	[5]
Phloretin	DMYA50U	Discovery agent	N.A.	Investigative	[4]

Experimental Enzyme Kinetic Data of Drugs

Drug Name	Indication	Highest Status	Kinetic Data	REF
Chrysin	Discovery agent [N.A.]	Investigative	Km = 0.004 microM	[4]
Phloretin	Discovery agent [N.A.]	Investigative	Km = 0.0068 microM	[4]
Eugenol	Discovery agent [N.A.]	Patented	Km = 0.0084 microM	[4]
Afimoxifene	Breast cancer [2C60-2C65]	Phase 2	Km = 0.004 microM	[5]
Curcumin	Solid tumour/cancer [2A00-2F9Z]	Phase 3	Km = 0.1 microM	[4]

References

• [1] Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):747-759.
• [2] Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.
• [3] Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy. Future Oncol. 2010 Apr;6(4):563-85.
• [4] 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.
• [5] Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2006-14.