m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG00636)
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
    Click to Show/Hide
Status
Approved
Structure
Formula
C18H19ClN4
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
PubChem CID
135398737
VARIDT Drug ID
DR00474
INTEDE Drug ID
DR0363
Target Gene(s) and Their Upstream m6A Regulator, Together with the Effect of Target Gene(s) in Drug Response
The target genes involved in drug-target interaction (such as drug-metabolizing enzymes, drug transporters and therapeutic targets) and drug-mediated cell death signaling (including modulating DNA damage and repair capacity, escaping from drug-induced apoptosis, autophagy, cellular metabolic reprogramming, oncogenic bypass signaling, cell microenvironment, cell stemness, etc.) could be regulated by m6A regulator(s) and affected their corresponding drug response. You can browse detailed information on drug-related target gene(s) mediated by m6A regulators.
Cytochrome P450 2C8 (CYP2C8)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for Clozapine. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of Clozapine through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for Clozapine. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of Clozapine through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for Clozapine. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Clozapine through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
YTH domain-containing protein 2 (YTHDC2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for Clozapine. The YTH domain-containing protein 2 (YTHDC2) has potential in affecting the response of Clozapine through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
P-glycoprotein 1 (ABCB1)
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary P-glycoprotein 1 (ABCB1) is a therapeutic target for Clozapine. The Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has potential in affecting the response of Clozapine through regulating the expression of P-glycoprotein 1 (ABCB1). [3], [4]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary P-glycoprotein 1 (ABCB1) is a therapeutic target for Clozapine. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Clozapine through regulating the expression of P-glycoprotein 1 (ABCB1). [4], [5]
References
Ref 1 Methylation of adenosine at the N(6) position post-transcriptionally regulates hepatic P450s expression. Biochem Pharmacol. 2020 Jan;171:113697. doi: 10.1016/j.bcp.2019.113697. Epub 2019 Nov 7.
Ref 2 Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):592-9. doi: 10.1007/pl00005298.
Ref 3 Binding of RNA m6A by IGF2BP3 triggers chemoresistance of HCT8 cells via upregulation of ABCB1. Am J Cancer Res. 2021 Apr 15;11(4):1428-1445. eCollection 2021.
Ref 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. doi: 10.1211/0022357043969.
Ref 5 METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. Exp Mol Med. 2021 Jan;53(1):91-102. doi: 10.1038/s12276-020-00510-w. Epub 2021 Jan 8.