Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMFC71L)

Drug Name

Clozapine Drug Info

Synonyms

Asaleptin; CLOZARIL; Clorazil; Clozapin; Clozapina; Clozapinum; Fazaclo; Iprox; Leponex; Lepotex; Fazaclo ODT; C 6305; HF1854; Clopine (TN); Clozapina [INN-Spanish]; Clozapine(tautomer); Clozapinum [INN-Latin]; Clozaril (TN); Denzapine (TN); Fazaclo (TN); Froidir (TN); HF-1854; KS-1166; Klozapol (TN); LEX-123; LX 100-129; Leponex (TN); W-801; Zaponex (TN); Clozapine [USAN:INN:BAN]; Clozapine (JAN/USP/INN); 3-chloro-6-(4-methylpiperazin-1-yl)-5H-benzo[b][1,4]benzodiazepine; 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-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-methyl-piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine; 8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine

Indication

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Approved	[1]
Treatment-refractory schizophrenia		Investigative	[2]

Therapeutic Class

Antipsychotic Agents

Cross-matching ID

PubChem CID: 135398737
ChEBI ID: CHEBI:3766
CAS Number: CAS 5786-21-0
TTD Drug ID: DMFC71L
VARIDT Drug ID: DR00474
INTEDE Drug ID: DR0363
ACDINA Drug ID: D00145

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D4 receptor (D4R)	TTE0A2F	DRD4_HUMAN	Modulator	[3]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Approved	[6]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Approved	[7]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Approved	[5]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Approved	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Approved	[9]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Approved	[7]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Dopamine D4 receptor (D4R)	DTT	DRD4	2.138	1.766	1.322	1
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	9.791	3.744	3.413	1.609
Cytochrome P450 2A6 (CYP2A6)	DME	CYP2A6	10.644	6.631	6.598	6.937
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	10.036	5.779	6.508	6.481
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.867	5.142	5.52	7.08
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	3.307	5.005	3.921	5.327
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	11.76	5.931	6.164	9.423
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Schizophrenia

ICD Disease Classification

6A20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D4 receptor (D4R)	DTT	DRD4	1.90E-01	0.19	0.76
P-glycoprotein 1 (ABCB1)	DTP	P-GP	6.54E-01	1.95E-01	4.04E-01
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	5.57E-01	-7.89E-02	-7.93E-01
Cytochrome P450 2A6 (CYP2A6)	DME	CYP2A6	8.99E-01	4.59E-03	2.19E-02
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	8.46E-01	-6.63E-03	-4.49E-02
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	9.62E-01	2.57E-02	1.10E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	2.35E-01	2.78E-02	2.09E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.76E-01	1.26E-01	8.27E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 38).
2	Clozapine FDA Label
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
4	Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates. J Pharm Pharmacol. 2004 Aug;56(8):967-75.
5	Drug metabolism and atypical antipsychotics. Eur Neuropsychopharmacol. 1999 Jun;9(4):301-9.
6	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.
7	Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):592-9.
8	Characterization of human cytochrome P450s involved in the bioactivation of clozapine. Drug Metab Dispos. 2013 Mar;41(3):651-8.
9	Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):4-22.