m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG03330)
Name
CYT-387
Synonyms
Cyt387; 1056634-68-4; MOMELOTINIB; Cyt-387; N-(Cyanomethyl)-4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)benzamide; CYT 387; CYT 11387; UNII-6O01GMS00P; N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide; 6O01GMS00P; CHEMBL1078178; AK102858; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide; CYT387 sulfate salt; N-(Cyanomethyl)-4-(2-((4-morpholinophenyl)-amino)pyrimidin-4-yl)benzamide
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Status
Phase 3
Structure
Formula
C23H22N6O2
InChI
1S/C23H22N6O2/c24-10-12-25-22(30)18-3-1-17(2-4-18)21-9-11-26-23(28-21)27-19-5-7-20(8-6-19)29-13-15-31-16-14-29/h1-9,11H,12-16H2,(H,25,30)(H,26,27,28)
InChIKey
ZVHNDZWQTBEVRY-UHFFFAOYSA-N
PubChem CID
25062766
TTD Drug ID
D0D5ZJ
INTEDE Drug ID
DR1880
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 CYT-387. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of CYT-387 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 CYT-387. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of CYT-387 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 CYT-387. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of CYT-387 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 CYT-387. The YTH domain-containing protein 2 (YTHDC2) has potential in affecting the response of CYT-387 through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
Janus kinase 2 (JAK-2)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for CYT-387. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of CYT-387 through regulating the expression of Janus kinase 2 (JAK-2). [3], [4]
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for CYT-387. The Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has potential in affecting the response of CYT-387 through regulating the expression of Janus kinase 2 (JAK-2). [4], [5]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for CYT-387. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of CYT-387 through regulating the expression of Janus kinase 2 (JAK-2). [4], [5]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for CYT-387. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of CYT-387 through regulating the expression of Janus kinase 2 (JAK-2). [4], [6]
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 Pharmacokinetics and Disposition of Momelotinib Revealed a Disproportionate Human Metabolite-Resolution for Clinical Development. Drug Metab Dispos. 2018 Mar;46(3):237-247. doi: 10.1124/dmd.117.078899. Epub 2018 Jan 8.
Ref 3 FTO inhibits UPR(mt)-induced apoptosis by activating JAK2/STAT3 pathway and reducing m6A level in adipocytes. Apoptosis. 2021 Aug;26(7-8):474-487. doi: 10.1007/s10495-021-01683-z. Epub 2021 Jul 1.
Ref 4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 5 N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1. Front Cell Dev Biol. 2021 Dec 7;9:731810. doi: 10.3389/fcell.2021.731810. eCollection 2021.
Ref 6 ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer. J Exp Clin Cancer Res. 2021 Sep 8;40(1):284. doi: 10.1186/s13046-021-02088-1.