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

General Information of Drug (ID: DR0363)
Drug Name
Clozapine
Synonyms
Clorazil; Clozapin; Clozapina; Clozapina [INN-Spanish]; Clozapinum; Clozapinum [INN-Latin]; Fazaclo; Fazaclo ODT; HF 1854; Asaleptin; CLOZARIL; HF-1854; LX 100-129; Leponex; Lepotex; clozapine; 5786-21-0; 5H-Dibenzo[b,e][1,4]diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-; 8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine; 8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine; 8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine; CCRIS 9171; HSDB 6478; Iprox; UNII-J60AR2IKIC; W-801
Indication Schizophrenia [ICD11: 6A20] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 326.8 Topological Polar Surface Area 30.9
Heavy Atom Count 23 Rotatable Bond Count 1
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
135398737
ChEBI ID
CHEBI:3766
CAS Number
5786-21-0
TTD Drug ID
D0Z1RV
Formula
C18H19ClN4
Canonical SMILES
CN1CCN(CC1)C2=NC3=C(C=CC(=C3)Cl)NC4=CC=CC=C42
InChI
1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3
InChIKey
QZUDBNBUXVUHMW-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
Clozapine glucuronide DM001493
131769989
Conjugation - Glucuronidation 1 [8]
Clozapine N-oxide DM001492
135445691
Oxidation - N-Oxidation 1 [9]
N-desmethylclozapine DM001491
135409468
Oxidation - N-demethlylation 1 [3]
N-desmethylclozapine DM001491
135409468
Oxidation - N-Demethylation 1 [9]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002835 Clozapine N-desmethylclozapine Oxidation - N-Demethylation CYP3A4 ... [9]
MR002836 Clozapine Clozapine N-oxide Oxidation - N-Oxidation CYP3A4 ... [9]
MR002837 Clozapine Clozapine glucuronide Conjugation - Glucuronidation UGT1A4 [8]
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 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_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
[4]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[5]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[6]
Dimethylaniline oxidase 3 (FMO3) DME0039 Homo sapiens
FMO3_HUMAN
1.14.13.8
[7]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[6]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[8]
⏷ Show the Full List of 9  DME(s)
References
1 Clozapine was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):4-22.
3 Characterization of human cytochrome P450s involved in the bioactivation of clozapine. Drug Metab Dispos. 2013 Mar;41(3):651-8.
4 Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):592-9.
5 Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro: preferential inhibition of CYP2D6. Drug Metab Dispos. 1999 Sep;27(9):1078-84.
6 Drug metabolism and atypical antipsychotics. Eur Neuropsychopharmacol. 1999 Jun;9(4):301-9.
7 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.
8 DrugBank(Pharmacology-Metabolism)Clozapine
9 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.

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