m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG02877)
Name
R547
Synonyms
LIA; R-547; [4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone
    Click to Show/Hide
Status
Discontinued in Phase 1
Structure
Formula
C18H21F2N5O4S
InChI
1S/C18H21F2N5O4S/c1-29-13-4-3-12(19)15(20)14(13)16(26)11-9-22-18(24-17(11)21)23-10-5-7-25(8-6-10)30(2,27)28/h3-4,9-10H,5-8H2,1-2H3,(H3,21,22,23,24)
InChIKey
JRNJNYBQQYBCLE-UHFFFAOYSA-N
PubChem CID
6918852
TTD Drug ID
D04FHB
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
 Regulator Info 
Response Summary Cyclin-dependent kinase 1 (CDK1) is a therapeutic target for R547. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of R547 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
 Regulator Info 
Response Summary Cyclin-dependent kinase 1 (CDK1) is a therapeutic target for R547. The Protein virilizer homolog (VIRMA) has potential in affecting the response of R547 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
 Regulator Info 
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for R547. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of R547 through regulating the expression of Cyclin-dependent kinase 2 (CDK2). [2], [4]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for R547. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of R547 through regulating the expression of Cyclin-dependent kinase 2 (CDK2). [2], [5]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for R547. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of R547 through regulating the expression of Cyclin-dependent kinase 2 (CDK2). [2], [4]
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
 Regulator Info 
Response Summary Cyclin-dependent kinase 4 (CDK4) is a therapeutic target for R547. The Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has potential in affecting the response of R547 through regulating the expression of Cyclin-dependent kinase 4 (CDK4). [2], [6]
Protein virilizer homolog (VIRMA)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cyclin-dependent kinase 4 (CDK4) is a therapeutic target for R547. The Protein virilizer homolog (VIRMA) has potential in affecting the response of R547 through regulating the expression of Cyclin-dependent kinase 4 (CDK4). [2], [6]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cyclin-dependent kinase 4 (CDK4) is a therapeutic target for R547. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of R547 through regulating the expression of Cyclin-dependent kinase 4 (CDK4). [2], [5]
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 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 6 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.