General Information of the Drug (ID: M6APDG02013)
Name
PHA-793887
Synonyms
Cyclin-dependent kinase inhibitor (cancer), Nerviano
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Status
Phase 1
Structure
Formula
C19H31N5O2
InChI
1S/C19H31N5O2/c1-12(2)10-15(25)20-17-14-11-24(19(3,4)16(14)21-22-17)18(26)13-6-8-23(5)9-7-13/h12-13H,6-11H2,1-5H3,(H2,20,21,22,25)
InChIKey
HUXYBQXJVXOMKX-UHFFFAOYSA-N
PubChem CID
46191454
TTD Drug ID
D0P1CV
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.
Cyclin-dependent kinase 1 (CDK1)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 1 (CDK1) is a therapeutic target for PHA-793887. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 1 (CDK1). [1], [2]
Protein virilizer homolog (VIRMA)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 1 (CDK1) is a therapeutic target for PHA-793887. The Protein virilizer homolog (VIRMA) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 1 (CDK1). [2], [3]
Cyclin-dependent kinase 2 (CDK2)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for PHA-793887. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 2 (CDK2). [4], [5]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for PHA-793887. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 2 (CDK2). [5], [6]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for PHA-793887. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 2 (CDK2). [4], [5]
Cyclin-dependent kinase 4 (CDK4)
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 4 (CDK4) is a therapeutic target for PHA-793887. The Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 4 (CDK4). [7], [8]
Protein virilizer homolog (VIRMA)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 4 (CDK4) is a therapeutic target for PHA-793887. The Protein virilizer homolog (VIRMA) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 4 (CDK4). [7], [8]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
Response Summary Cyclin-dependent kinase 4 (CDK4) is a therapeutic target for PHA-793887. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of PHA-793887 through regulating the expression of Cyclin-dependent kinase 4 (CDK4). [6], [8]
References
Ref 1 CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression. Int J Biol Sci. 2021 Mar 15;17(5):1178-1190. doi: 10.7150/ijbs.57783. eCollection 2021.
Ref 2 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. doi: 10.1038/nrd2907.
Ref 3 KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner. Oncogene. 2019 Aug;38(33):6123-6141. doi: 10.1038/s41388-019-0861-z. Epub 2019 Jul 8.
Ref 4 FTO regulates adipogenesis by controlling cell cycle progression via m(6)A-YTHDF2 dependent mechanism. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Oct;1863(10):1323-1330. doi: 10.1016/j.bbalip.2018.08.008. Epub 2018 Aug 13.
Ref 5 Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45. doi: 10.1182/blood-2008-12-190256. Epub 2009 Feb 20.
Ref 6 YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat Commun. 2019 Oct 25;10(1):4892. doi: 10.1038/s41467-019-12801-6.
Ref 7 Identification of pathology-specific regulators of m(6)A RNA modification to optimize lung cancer management in the context of predictive, preventive, and personalized medicine. EPMA J. 2020 Jul 29;11(3):485-504. doi: 10.1007/s13167-020-00220-3. eCollection 2020 Sep.
Ref 8 ClinicalTrials.gov (NCT04557449) Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (CDK4). U.S. National Institutes of Health.