m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG02490)
Name
GSK-677954
Synonyms
SCHEMBL2065429
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Status
Discontinued in Phase 2
Structure
Formula
C34H36F3N3O4S2
InChI
1S/C34H36F3N3O4S2/c1-4-33(5-2,32(41)42)44-27-14-16-28(17-15-27)45-22-29-30(38-31(46-29)23-6-8-24(9-7-23)34(35,36)37)40-20-18-39(19-21-40)25-10-12-26(43-3)13-11-25/h6-17H,4-5,18-22H2,1-3H3,(H,41,42)
InChIKey
COHCTXOFKQXTRQ-UHFFFAOYSA-N
PubChem CID
56603715
TTD Drug ID
D0S6KX
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.
Peroxisome proliferator-activated receptor alpha (PPARA)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Peroxisome proliferator-activated receptor alpha (PPARA) is a therapeutic target for GSK-677954. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of GSK-677954 through regulating the expression of Peroxisome proliferator-activated receptor alpha (PPARA). [1], [2]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Peroxisome proliferator-activated receptor alpha (PPARA) is a therapeutic target for GSK-677954. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of GSK-677954 through regulating the expression of Peroxisome proliferator-activated receptor alpha (PPARA). [2], [3]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Peroxisome proliferator-activated receptor alpha (PPARA) is a therapeutic target for GSK-677954. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of GSK-677954 through regulating the expression of Peroxisome proliferator-activated receptor alpha (PPARA). [2], [4]
Wilms tumor 1-associating protein (WTAP)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Peroxisome proliferator-activated receptor alpha (PPARA) is a therapeutic target for GSK-677954. The Wilms tumor 1-associating protein (WTAP) has potential in affecting the response of GSK-677954 through regulating the expression of Peroxisome proliferator-activated receptor alpha (PPARA). [2], [3]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Peroxisome proliferator-activated receptor alpha (PPARA) is a therapeutic target for GSK-677954. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of GSK-677954 through regulating the expression of Peroxisome proliferator-activated receptor alpha (PPARA). [2], [4]
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a therapeutic target for GSK-677954. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of GSK-677954 through regulating the expression of Peroxisome proliferator-activated receptor gamma (PPAR-gamma). [5], [6]
References
Ref 1 Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation. Front Pharmacol. 2020 Dec 18;11:568006. doi: 10.3389/fphar.2020.568006. eCollection 2020.
Ref 2 Modulation of PPAR receptor subtype selectivity of the ligands: aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6471-5. doi: 10.1016/j.bmcl.2008.10.062. Epub 2008 Oct 17.
Ref 3 A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014 Feb;10(2):93-5. doi: 10.1038/nchembio.1432. Epub 2013 Dec 6.
Ref 4 Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m(6)A mRNA Methylation. Cell Rep. 2018 Nov 13;25(7):1816-1828.e4. doi: 10.1016/j.celrep.2018.10.068.
Ref 5 The m(6)A demethylase FTO promotes the osteogenesis of mesenchymal stem cells by downregulating PPARG. Acta Pharmacol Sin. 2022 May;43(5):1311-1323. doi: 10.1038/s41401-021-00756-8. Epub 2021 Aug 30.
Ref 6 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008.