Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1717)
Drug Name
Warfarin sodium
Synonyms
Warcoumin; Warfarin sodium; Warfarin sodium [USP]; Warfarin sodium salt; Warfarin, sodium salt; Warfilone; Zoocoumarin sodium salt; Warfarat; Warfarine; Zoocoumarin; mice bait; Warfarin; 81-81-2; Athrombine-K; Brumolin; Coumadin; Coumafen; Coumafene; Coumaphene; Coumarins; Coumefene; D-Con; Dethmor; Dethnel; Frass-Ratron; Kumader; Kumadu; Kumatox; Kypfarin; Maag Rattentod Cum; Mar-Frin; Martin's mar-frin; Maveran; Panwarfin; Prothromadin; Rat & Rat-B-gon; Rat-Gard; Rat-Kill; Rat-Mix; Rat-Ola; Rat-Trol; Rat-a-way; Ratorex; Ratoxin; Ratron; Rats-no-more; Ratten-Koederrohr; Rattentraenke; Rattunal; Ro-Deth; Rodafarin; Rosex; Solfarin; Temus W; Tox-hid; Vampirinip II; Vampirinip iii; (+-)-Warfarin sodium; 129-06-6; Aldocumar; Athrombin; C19H15NaO4; Caswell No. 903A; Coumadan Sodico; Coumadin sodium; Coumadine; Coumafene sodium; Dicusat; EINECS 204-929-4; EPA Pesticide Chemical Code 086003; Jantoven; Marevam; Marevan; Orfarin; Ratsul soluble; Simarc; Sodium 2-oxo-3-(3-oxo-1-phenylbutyl)-2H-chromen-4-olate; Sodium coumadin; Sodium warfarin; Tintorane; UniWarfin; Varfine; Waran
Indication Atrial fibrillation [ICD11: BC81] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 330.3 Topological Polar Surface Area 66.4
Heavy Atom Count 24 Rotatable Bond Count 4
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 4
Cross-matching ID
PubChem CID
16204922
ChEBI ID
CHEBI:90911
CAS Number
914462-92-3
TTD Drug ID
D0E3OF
Formula
C19H15NaO4
Canonical SMILES
CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OCC2(CCC3(CCC(=O)N3)CN2)C4=CC=CC=C4.O.Cl
InChI
1S/C25H26F6N2O2.ClH.H2O/c1-16(17-11-19(24(26,27)28)13-20(12-17)25(29,30)31)35-15-23(18-5-3-2-4-6-18)10-9-22(14-32-23)8-7-21(34)33-22;;/h2-6,11-13,16,32H,7-10,14-15H2,1H3,(H,33,34);1H;1H2/t16-,22-,23-;;/m1../s1
InChIKey
KYITYFHKDODNCQ-UHFFFAOYSA-M
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
(R)9-hydroxywarfarin DM005318 N. A. Oxidation - 9-hydroxylation 1 [10] , [11]
(S)9-hydroxywarfarin DM005319 N. A. Oxidation - 9-hydroxylation 1 [10] , [11]
R-10(R)-Hydroxywarfarin DM005303
54742172
Oxidation - 10-hydroxylation 1 [10] , [11]
R-10(S)-Hydroxywarfarin DM005306
54744202
Oxidation - 10-hydroxylation 1 [10] , [11]
R-4'-Hydroxywarfarin DM005310
54717351
Oxidation - 4'-hydroxylation 1 [10] , [11]
R-6-Hydroxywarfarin DM005312
54750067
Oxidation - 6-hydroxylation 1 [10] , [11]
R-7-Hydroxywarfarin DM005307
54732122
Oxidation - 7-hydroxylation 1 [10] , [11]
R-8-Hydroxywarfarin DM005316
54744201
Oxidation - 8-hydroxylation 1 [10] , [11]
R-Warfarin-R-Alcohol DM005320
54723890
Reduction - Reduction 1 [10] , [11]
R-Warfarin-S-Alcohol DM005321 N. A. Reduction - Reduction 1 [10] , [11]
S-4'-Hydroxywarfarin DM005315
54717350
Oxidation - 4'-hydroxylation 1 [10] , [11]
S-6-Hydroxywarfarin DM005314
54731323
Oxidation - 6-hydroxylation 1 [10] , [11]
S-7-Hydroxywarfarin DM005317
54692246
Oxidation - 7-hydroxylation 1 [10] , [11]
S-Warfarin-R-Alcohol DM005322 N. A. Reduction - Reduction 1 [10] , [11]
S-Warfarin-S-Alcohol DM005323 N. A. Reduction - Reduction 1 [10] , [11]
(E)-dehydrowarfarin DM005304
54684422
Other reaction - Elimination 2 [10] , [11]
R-4'-Hydroxywarfarin glucuronide metabolite DM005311 N. A. Conjugation - Glucuronidation 2 [10] , [11]
R-6-Hydroxywarfarin sulfate DM005313 N. A. Conjugation - Sulfation 2 [10] , [11]
R-7-Hydroxywarfarin glucuronide metabolite DM005309 N. A. Conjugation - Glucuronidation 2 [10] , [11]
R-7-Hydroxywarfarin sulfate DM005308 N. A. Conjugation - Sulfation 2 [10] , [11]
(Z)-dehydrowarfarin DM005305
54704732
Other reaction - Elimination 3 [10] , [11]
⏷ Show the Full List of 21  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR013253 Warfarin sodium R-10(R)-Hydroxywarfarin Oxidation - 10-hydroxylation CYP3A4 [10], [11]
MR013256 Warfarin sodium R-10(S)-Hydroxywarfarin Oxidation - 10-hydroxylation CYP3A4 [10], [11]
MR013258 Warfarin sodium R-7-Hydroxywarfarin Oxidation - 7-hydroxylation CYP1A2 ... [10], [11]
MR013261 Warfarin sodium R-4'-Hydroxywarfarin Oxidation - 4'-hydroxylation CYP2C8 ... [10], [11]
MR013263 Warfarin sodium R-6-Hydroxywarfarin Oxidation - 6-hydroxylation CYP1A2 ... [10], [11]
MR013265 Warfarin sodium S-6-Hydroxywarfarin Oxidation - 6-hydroxylation CYP2C9 [10], [11]
MR013266 Warfarin sodium S-4'-Hydroxywarfarin Oxidation - 4'-hydroxylation CYP2C19 ... [10], [11]
MR013267 Warfarin sodium R-8-Hydroxywarfarin Oxidation - 8-hydroxylation CYP1A2 ... [10], [11]
MR013268 Warfarin sodium S-7-Hydroxywarfarin Oxidation - 7-hydroxylation CYP2C9 [10], [11]
MR013269 Warfarin sodium (R)9-hydroxywarfarin Oxidation - 9-hydroxylation Unclear [10], [11]
MR013270 Warfarin sodium (S)9-hydroxywarfarin Oxidation - 9-hydroxylation Unclear [10], [11]
MR013271 Warfarin sodium R-Warfarin-R-Alcohol Reduction - Reduction Unclear [10], [11]
MR013272 Warfarin sodium R-Warfarin-S-Alcohol Reduction - Reduction Unclear [10], [11]
MR013273 Warfarin sodium S-Warfarin-R-Alcohol Reduction - Reduction Unclear [10], [11]
MR013274 Warfarin sodium S-Warfarin-S-Alcohol Reduction - Reduction Unclear [10], [11]
MR013254 R-10(R)-Hydroxywarfarin (E)-dehydrowarfarin Other reaction - Elimination Unclear [10], [11]
MR013257 R-10(S)-Hydroxywarfarin (E)-dehydrowarfarin Other reaction - Elimination Unclear [10], [11]
MR013262 R-4'-Hydroxywarfarin R-4'-Hydroxywarfarin glucuronide metabolite Conjugation - Glucuronidation Unclear [10], [11]
MR013264 R-6-Hydroxywarfarin R-6-Hydroxywarfarin sulfate Conjugation - Sulfation Unclear [10], [11]
MR013259 R-7-Hydroxywarfarin R-7-Hydroxywarfarin sulfate Conjugation - Sulfation Unclear [10], [11]
MR013260 R-7-Hydroxywarfarin R-7-Hydroxywarfarin glucuronide metabolite Conjugation - Glucuronidation Unclear [10], [11]
MR013255 (E)-dehydrowarfarin (Z)-dehydrowarfarin Other reaction - Elimination Unclear [10], [11]
⏷ Show the Full List of 22 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C18 (CYP2C18) DME0017 Homo sapiens
CP2CI_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[5]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[6]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[2]
Sulfotransferase 1A1 (SULT1A1) DME0008 Homo sapiens
ST1A1_HUMAN
2.8.2.1
[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[8]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [9]
⏷ Show the Full List of 10  DME(s)
References
1 Warfarin Sodium was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Metabolism of R- and S-warfarin by CYP2C19 into four hydroxywarfarins. Drug Metab Lett. 2012 Sep 1;6(3):157-64.
3 Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74.
4 Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol. 1997;52(4):293-8.
5 Pharmacogenomics of CYP2C9: functional and clinical considerations. J Pers Med. 2017 Dec 28;8(1).
6 Contribution of three CYP3A isoforms to metabolism of R- and S-warfarin. Drug Metab Lett. 2010 Dec;4(4):213-9.
7 Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Phytomedicine. 2001 Nov;8(6):481-8.
8 Assessing cytochrome P450 and UDP-glucuronosyltransferase contributions to warfarin metabolism in humans. Chem Res Toxicol. 2009 Jul;22(7):1239-45.
9 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
10 Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46.
11 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. doi: 10.2174/092986709789057635.

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