m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG00405)
Name
PF-228
Synonyms
869288-64-2; PF-573228; PF 573228; PF573228; PF-228; CHEMBL514554; 3,4-Dihydro-6-[[4-[[[3-(methylsulfonyl)phenyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2(1H)-quinolinone; 6-((4-((3-(Methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; 6-[4-(3-Methanesulfonyl-benzylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3,4-dihydro-1H-quinolin-2-one
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Status
Investigative
Structure
Formula
C22H20F3N5O3S
InChI
1S/C22H20F3N5O3S/c1-34(32,33)16-4-2-3-13(9-16)11-26-20-17(22(23,24)25)12-27-21(30-20)28-15-6-7-18-14(10-15)5-8-19(31)29-18/h2-4,6-7,9-10,12H,5,8,11H2,1H3,(H,29,31)(H2,26,27,28,30)
InChIKey
HESLKTSGTIBHJU-UHFFFAOYSA-N
PubChem CID
11612883
TTD Drug ID
D02QAZ
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 PF-228. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of PF-228 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 PF-228. The Protein virilizer homolog (VIRMA) has potential in affecting the response of PF-228 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 PF-228. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of PF-228 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
 Regulator Info 
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for PF-228. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of PF-228 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
 Regulator Info 
Response Summary Cyclin-dependent kinase 2 (CDK2) is a therapeutic target for PF-228. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of PF-228 through regulating the expression of Cyclin-dependent kinase 2 (CDK2). [4], [5]
Focal adhesion kinase 1 (FAK)
Wilms tumor 1-associating protein (WTAP)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Focal adhesion kinase 1 (FAK) is a therapeutic target for PF-228. The Wilms tumor 1-associating protein (WTAP) has potential in affecting the response of PF-228 through regulating the expression of Focal adhesion kinase 1 (FAK). [7], [8]
Glycogen synthase kinase-3 beta (GSK-3B)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Glycogen synthase kinase-3 beta (GSK-3B) is a therapeutic target for PF-228. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of PF-228 through regulating the expression of Glycogen synthase kinase-3 beta (GSK-3B). [9], [10]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Glycogen synthase kinase-3 beta (GSK-3B) is a therapeutic target for PF-228. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of PF-228 through regulating the expression of Glycogen synthase kinase-3 beta (GSK-3B). [10], [11]
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Inhibitor of nuclear factor kappa-B kinase beta (IKKB) is a therapeutic target for PF-228. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of PF-228 through regulating the expression of Inhibitor of nuclear factor kappa-B kinase beta (IKKB). [12], [13]
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 Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidine derivatives. Eur J Med Chem. 2010 Jan;45(1):379-86. doi: 10.1016/j.ejmech.2009.10.002. Epub 2009 Oct 13.
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 Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. Eur J Med Chem. 2010 Mar;45(3):1158-66. doi: 10.1016/j.ejmech.2009.12.026. Epub 2009 Dec 21.
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 WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer. Cancer Lett. 2019 Jun 1;451:48-57. doi: 10.1016/j.canlet.2019.02.043. Epub 2019 Mar 6.
Ref 8 A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9. doi: 10.4161/15384101.2014.949550.
Ref 9 Vascular Smooth Muscle FTO Promotes Aortic Dissecting Aneurysms via m6A Modification of Klf5. Front Cardiovasc Med. 2020 Nov 20;7:592550. doi: 10.3389/fcvm.2020.592550. eCollection 2020.
Ref 10 Rational design of potent GSK3beta inhibitors with selectivity for Cdk1 and Cdk2. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1985-9. doi: 10.1016/j.bmcl.2010.01.114. Epub 2010 Jan 25.
Ref 11 N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022 May 13;13(1):2672. doi: 10.1038/s41467-022-30217-7.
Ref 12 The m(6)A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-KappaB/MYC signaling network. Oncogene. 2019 May;38(19):3667-3680. doi: 10.1038/s41388-019-0683-z. Epub 2019 Jan 18.
Ref 13 Company report (Millennium)