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Drug-Target Interaction

Drug

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PubChem ID:2789
Structure:
Synonyms:
1-phenyl-5-methyl-8-chloro-1,2,4,5- tetrahydro-2,4-diketo-3H-1,5-benzodiazepine
1-Phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-diketo-3H-1,5-benzodiazepine
1-Phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1, 5-benzodiazepine
1-Phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazep
1-Phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazepine
1H-1,5-Benzodiazepine-2,4(3H,5H)-dione, 7-chloro-1-methyl-5-phenyl-
22316-47-8
5-24-08-00034 (Beilstein Handbook Reference)
7-Chloro-1-methyl-5-phenyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione
7-Chloro-1-methyl-5-phenyl-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione
8-chloro-5-methyl-1-phenyl-1,5-benzodiazepine-2,4-dione
AIDS-129201
AIDS129201
Ambap5118
BRN 0758410
C16H13ClN2O2
C8414_SIGMA
CCRIS 7506
CHEBI:31413
Chlorepin
CLOBAZAM
Clobazam (JAN/USAN/INN)
Clobazam [USAN:BAN:INN]
Clobazamum
Clobazamum [INN-Latin]
Clorepin
D01253
DB00349
DEA No. 2751
EINECS 244-908-7
Frisium
H 4723
H-4723
HR 376
LM 2717
LM-2717
LS-34098
Mystan
Mystan (TN)
NCGC00168249-01
nchembio747-comp39
NSC 336279
NSC336279
RU-4723
Urbadan
Urbanyl
WLN: T67 GNV JVN IHJ CG G1 KR
ZINC00001175
ATC-Codes:

Target

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Uniprot ID:CP2CJ_HUMAN
Synonyms:
(R)-limonene 6-monooxygenase
(S)-limonene 6-monooxygenase
(S)-limonene 7-monooxygenase
CYPIIC17
CYPIIC19
Cytochrome P450 2C19
Mephenytoin 4-hydroxylase
P450-11A
P450-254C
EC-Numbers:1.14.13.48
1.14.13.49
1.14.13.80
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----
----

References:

12451290
14729419
15483195
In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19.. Carole Giraud; Agnès Tran; Elisabeth Rey; Jean Vincent; Jean-Marc Tréluyer; Gérard Pons (2004) Drug metabolism and disposition: the biological fate of chemicals display abstract
The specific cytochrome P450 (P450) isoforms mediating the biotransformations of clobazam (CLB) and those of its major metabolites, N-desmethylclobazam (NCLB) and 4'-hydroxyclobazam were identified using cDNA-expressed P450 and P450-specific chemical inhibitors. Among the 13 cDNA-expressed P450 isoforms tested, CLB was mainly demethylated by CYP3A4, CYP2C19, and CYP2B6 and 4'-hydroxylated by CYP2C19 and CYP2C18. CYP2C19 and CYP2C18 catalyzed the 4'-hydroxylation of NCLB. The kinetics of the major biotransformations were studied: CYP3A4, CYP2C19, and CYP2B6 mediated the formation of NCLB with Km = 29.0, 31.9, and 289 microM, Vmax = 6.20, 1.15, and 5.70 nmol/min/nmol P450, and intrinsic clearance (CLint) = 214, 36.1, and 19.7 microl/min/nmol P450, respectively. NCLB was hydroxylated to 4'-hydroxydesmethylclobazam by CYP2C19 with Km = 5.74 microM, Vmax = 0.219 nmol/min/nmol P450, and CLint = 38.2 microl/min/nmol P450 (Hill coefficient = 1.54). These findings were supported by chemical inhibition studies in human liver microsomes. Indeed, ketoconazole (1 microM) inhibited the demethylation of CLB by 70% and omeprazole (10 microM) by 19%; omeprazole inhibited the hydroxylation of NCLB by 26%. Twenty-two epileptic patients treated with CLB were genotyped for CYP2C19. The NCLB/CLB plasma metabolic ratio was significantly higher in the subjects carrying one CYP2C19*2 mutated allele than in those carrying the wild-type genotype. CYP3A4 and CYP2C19 are the main P450s involved in clobazam metabolism. Interactions with other drugs metabolized by these P450s can occur; moreover, the CYP2C19 genetic polymorphism could be responsible for interindividual variations of plasma concentrations of N-desmethylclobazam and thus for occurrence of adverse events.
15533655