m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG02915)
Name
RXDX-106
Synonyms
CEP-40783; 1437321-24-8; CEP40783; UNII-1969ZJE05Q; 1969ZJE05Q; N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3-(4-fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide; N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide; RXDX-106 (CEP-40783); SCHEMBL16089863; BCP25839; EX-A2540; MFCD28502441; NSC797770; s8570; AKOS032960472; ZINC205893112; CCG-270157; CS-6371; NSC-797770; SB18930; AC-31425; AS-35141; HY-100946; N-(4-((6,7-Dimethoxy-4-quinolinyl)oxy)-3-fluorophenyl)-3-(4-fluorophenyl)-1,2,3,4-tetrahydro-1-(1-methylethyl)-2,4-dioxo-5-pyrimidinecarboxamide
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Status
Phase 1
Structure
Formula
C31H26F2N4O6
InChI
1S/C31H26F2N4O6/c1-17(2)36-16-22(30(39)37(31(36)40)20-8-5-18(32)6-9-20)29(38)35-19-7-10-26(23(33)13-19)43-25-11-12-34-24-15-28(42-4)27(41-3)14-21(24)25/h5-17H,1-4H3,(H,35,38)
InChIKey
FKCWHHYUMFGOPY-UHFFFAOYSA-N
PubChem CID
71576419
TTD Drug ID
D7HZ3T
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.
Proto-oncogene c-Met (MET)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Proto-oncogene c-Met (MET) is a therapeutic target for RXDX-106. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RXDX-106 through regulating the expression of Proto-oncogene c-Met (MET). [1], [2]
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 RXDX-106. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of RXDX-106 through regulating the expression of Tyrosine-protein kinase Mer (MERTK). [3], [4]
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 RXDX-106. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of RXDX-106 through regulating the expression of Tyrosine-protein kinase Mer (MERTK). [3], [4]
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 RXDX-106. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RXDX-106 through regulating the expression of Tyrosine-protein kinase UFO (AXL). [5], [6]
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 RXDX-106. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of RXDX-106 through regulating the expression of Tyrosine-protein kinase UFO (AXL). [6], [7]
References
Ref 1 RNA m(6) A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c-Met. J Cell Physiol. 2020 Oct;235(10):7107-7119. doi: 10.1002/jcp.29608. Epub 2020 Feb 4.
Ref 2 TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors. Mol Oncol. 2020 Jan;14(1):54-68. doi: 10.1002/1878-0261.12600. Epub 2019 Dec 3.
Ref 3 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 4 The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016 Mar;1(3):e85630. doi: 10.1172/jci.insight.85630.
Ref 5 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 6 National Cancer Institute Drug Dictionary (drug name PF-07265807).
Ref 7 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.