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

General Information of Drug (ID: DR1282)
Drug Name
Phenytoin
Synonyms
Phanantin; Phanatine; Phenatine; Phenatoine; Phentytoin; Phenytoine; Sodantoin; Sodanton; Sylantoic; Thilophenyl; Aleviatin; Dantoinal; Di-Hydan; Difenin; Dihycon; Dihydantoin; Dilabid; Dilantin; Diphantoin; Diphedan; Diphenine; Diphentyn; Diphenylan; Diphenylhydantoin; Diphenylhydatanoin; Ditoinate; Elepsindon; Epamin; Epilantin; Fenitoina; Fenylepsin; Fenytoine; Hidantilo; Hidantina; Hidantomin; Hydantoinal; Kessodanten; Lehydan; Lepitoin; Zentronal; Zentropil; phenytoin; 5,5-DIPHENYLHYDANTOIN; 5,5-diphenylimidazolidine-2,4-dione; 57-41-0
Indication Epilepsy [ICD11: 8A60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 252.27 Topological Polar Surface Area 58.2
Heavy Atom Count 19 Rotatable Bond Count 2
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
1775
PubChem SID
9647 ; 74340 ; 592179 ; 596082 ; 841957 ; 3136997 ; 4284342 ; 5171921 ; 7847578 ; 7980312 ; 8151275 ; 10527886 ; 10589150 ; 11111069 ; 11335682 ; 11353793 ; 11360921 ; 11363999 ; 11366561 ; 11369123 ; 11371880 ; 11374526 ; 11377285 ; 11461893 ; 11485017 ; 11489097 ; 11490706 ; 11492799 ; 11494919 ; 11532994 ; 14847761 ; 17389903 ; 17404941 ; 24278370 ; 26068808 ; 26753026 ; 26753027 ; 26753028 ; 29220975 ; 46508847 ; 47588955 ; 47736431 ; 47736432 ; 47795039 ; 48168464 ; 48184955 ; 48243361 ; 48413692 ; 48416427 ; 48422573
ChEBI ID
CHEBI:8107
CAS Number
57-41-0
TTD Drug ID
D0E4DW
Formula
C15H12N2O2
Canonical SMILES
C1=CC=C(C=C1)C2(C(=O)NC(=O)N2)C3=CC=CC=C3
InChI
1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19)
InChIKey
CXOFVDLJLONNDW-UHFFFAOYSA-N
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
Phenytoin arene-oxide DM001248
101592230
Oxidation - Oxidation 1 [2]
Phenytoin dihydrodiol DM001254
152954
Oxidation - Dihydroxylation; Oxidation 1 [10]
Hydroxyphenytoin DM001249
17732
Unclear 2 [2]
Phenytoin catechol DM001250
169703
Unclear 2 [10]
4-hydroxyphenytoin o-glucuronide DM001253
91667680
Conjugation - O-Glucuronidation 3 [2] , [11]
Phenytoin catechol DM001250
169703
Oxidation - Oxidation 3 [2]
Phenytoin methylcatechol DM001251
131769979
Conjugation - Methylation 3 [2]
Phenytoin quinone DM001252
131769980
Oxidation - Oxidation 3 [2]
Phenytoin methylcatechol DM001251
131769979
Conjugation - Methylation 4 [2]
Phenytoin quinone DM001252
131769980
Oxidation - Oxidation 4 [2]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002035 Phenytoin Phenytoin arene-oxide Oxidation - Oxidation CYP2C9 ... [2]
MR002036 Phenytoin Phenytoin dihydrodiol Oxidation - Dihydroxylation; Oxidation CYP3A4 ... [10]
MR002029 Phenytoin arene-oxide Hydroxyphenytoin Unclear Unclear [2]
MR002034 Phenytoin dihydrodiol Phenytoin catechol Unclear Unclear [10]
MR002030 Hydroxyphenytoin Phenytoin catechol Oxidation - Oxidation CYP3A4 ... [2]
MR002031 Hydroxyphenytoin 4-hydroxyphenytoin o-glucuronide Conjugation - O-Glucuronidation UGT1A1 ... [2], [11]
MR002032 Phenytoin catechol Phenytoin methylcatechol Conjugation - Methylation COMT [2]
MR002033 Phenytoin catechol Phenytoin quinone Oxidation - Oxidation Unclear [2]
⏷ Show the Full List of 8 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Catechol O-methyltransferase (COMT) DME0043 Homo sapiens
COMT_HUMAN
2.1.1.6
[2]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[3]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C18 (CYP2C18) DME0017 Homo sapiens
CP2CI_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[6]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[2]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[7]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[4]
Epoxide hydrolase 1 (EPHX1) DME0623 Homo sapiens
HYEP_HUMAN
3.3.2.9
[3]
Glutathione S-transferase alpha-1 (GSTA1) DME0011 Homo sapiens
GSTA1_HUMAN
2.5.1.18
[8]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[5]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DME0072 Homo sapiens
UD16_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[2]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1365 Bacteroides dorei Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [9]
⏷ Show the Full List of 23  DME(s)
References
1 Phenytoin was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Pharmacogenomics knowledge for personalized medicine Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96.
3 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.
4 PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
5 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
6 Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010 Sep;8(3):254-67.
7 Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. J Acquir Immune Defic Syndr. 2004 Aug 15;36(5):1034-40.
8 Comparison of basal glutathione S-transferase activities and of the influence of phenobarbital, butylated hydroxy-anisole or 5,5'-diphenylhydantoin on enzyme activity in male rodents. Comp Biochem Physiol C. 1987;88(1):91-3.
9 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
10 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.
11 Biotransformation of phenytoin in the electrochemically-driven CYP2C19 system. Biophys Chem. 2022 Dec;291:106894. doi: 10.1016/j.bpc.2022.106894.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.