m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG03039)
Name
ONO-7475
Synonyms
1646839-59-9; UNII-0VCB95RHRV; N-(5-((6,7-Dimethoxyquinolin-4-yl)oxy)pyridin-2-yl)-2,5-dioxo-1-phenyl-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide; N-[5-[(6,7-Dimethoxy-4-quinolinyl)oxy]-2-pyridinyl]-1,2,5,6,7,8-hexahydro-2,5-dioxo-1-phenyl-3-quinolinecarboxamide; SCHEMBL16426362; ONO7475; BCP33232; MFCD32689448; s8933; ONO-7475; ONO 7475; HY-114358; CS-0083699; 3-Quinolinecarboxamide, N-(5-((6,7-dimethoxy-4-quinolinyl)oxy)-2-pyridinyl)-1,2,5,6,7,8-hexahydro-2,5-dioxo-1-phenyl-; N-[5-(6,7-dimethoxyquinolin-4-yl)oxypyridin-2-yl]-2,5-dioxo-1-phenyl-7,8-dihydro-6H-quinoline-3-carboxamide
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Status
Phase 1/2
Structure
Formula
C32H26N4O6
InChI
1S/C32H26N4O6/c1-40-28-16-21-24(17-29(28)41-2)33-14-13-27(21)42-20-11-12-30(34-18-20)35-31(38)23-15-22-25(9-6-10-26(22)37)36(32(23)39)19-7-4-3-5-8-19/h3-5,7-8,11-18H,6,9-10H2,1-2H3,(H,34,35,38)
InChIKey
WHMMKPWGWNYYFE-UHFFFAOYSA-N
PubChem CID
90645873
TTD Drug ID
DA1MG8
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.
Tyrosine-protein kinase Mer (MERTK)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Tyrosine-protein kinase Mer (MERTK) is a therapeutic target for ONO-7475. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of ONO-7475 through regulating the expression of Tyrosine-protein kinase Mer (MERTK). [1], [2]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Tyrosine-protein kinase Mer (MERTK) is a therapeutic target for ONO-7475. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of ONO-7475 through regulating the expression of Tyrosine-protein kinase Mer (MERTK). [1], [2]
Tyrosine-protein kinase UFO (AXL)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Tyrosine-protein kinase UFO (AXL) is a therapeutic target for ONO-7475. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of ONO-7475 through regulating the expression of Tyrosine-protein kinase UFO (AXL). [3], [4]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Tyrosine-protein kinase UFO (AXL) is a therapeutic target for ONO-7475. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of ONO-7475 through regulating the expression of Tyrosine-protein kinase UFO (AXL). [4], [5]
References
Ref 1 A dynamic N(6)-methyladenosine methylome regulates intrinsic and acquired resistance to tyrosine kinase inhibitors. Cell Res. 2018 Nov;28(11):1062-1076. doi: 10.1038/s41422-018-0097-4. Epub 2018 Oct 8.
Ref 2 Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46. doi: 10.1021/jm9009444.
Ref 3 METTL3 promotes ovarian carcinoma growth and invasion through the regulation of AXL translation and epithelial to mesenchymal transition. Gynecol Oncol. 2018 Nov;151(2):356-365. doi: 10.1016/j.ygyno.2018.09.015. Epub 2018 Sep 21.
Ref 4 AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells. J Thorac Oncol. 2020 Jun;15(6):973-999. doi: 10.1016/j.jtho.2020.01.015. Epub 2020 Feb 1.
Ref 5 Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis. Cell Stem Cell. 2020 Jul 2;27(1):81-97.e8. doi: 10.1016/j.stem.2020.04.001. Epub 2020 May 12.