General Information of the Drug (ID: M6APDG03888)
Name
PF-07265807
Synonyms
PF-5807; ARRY-067
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Status
Phase 1
TTD Drug ID
DP4KH3
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
Response Summary Tyrosine-protein kinase Mer (MERTK) is a therapeutic target for PF-07265807. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of PF-07265807 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
Response Summary Tyrosine-protein kinase Mer (MERTK) is a therapeutic target for PF-07265807. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of PF-07265807 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
Response Summary Tyrosine-protein kinase UFO (AXL) is a therapeutic target for PF-07265807. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of PF-07265807 through regulating the expression of Tyrosine-protein kinase UFO (AXL). [2], [3]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
Response Summary Tyrosine-protein kinase UFO (AXL) is a therapeutic target for PF-07265807. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of PF-07265807 through regulating the expression of Tyrosine-protein kinase UFO (AXL). [2], [4]
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 A Potent and Selective Dual Inhibitor of AXL and MERTK Possesses Both Immunomodulatory and Tumor-Targeted Activity. Front Oncol. 2020 Dec 7;10:598477. doi: 10.3389/fonc.2020.598477. eCollection 2020.
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 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.