m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG02670)
Name
GSK184072
Synonyms
Flutimide; 162666-34-4; AC1O5YLM; AKOS027326745; (5Z)-1-hydroxy-3-isobutyl-5-(2-methylpropylidene)pyrazine-2,6-dione; 2,6-(1H,3H)-Pyrazinedione, 1-hydroxy-5-(2-methylpropyl)-3-(2-methylpropylidene)-, (Z)-; 2,6-(1H,3H)-Pyrazinedione, 1-hydroxy-5-(2-methylpropyl)-3-(2-methylpropylidene)-, (3Z)-; (5Z)-1-hydroxy-3-(2-methylpropyl)-5-(2-methylpropylidene)pyrazine-2,6-dione
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Status
Discontinued in Phase 2
Structure
Formula
C12H18N2O3
InChI
1S/C12H18N2O3/c1-7(2)5-9-11(15)14(17)12(16)10(13-9)6-8(3)4/h5,7-8,17H,6H2,1-4H3/b9-5-
InChIKey
SIXHCCPAJIVTOY-UITAMQMPSA-N
PubChem CID
6443207
TTD Drug ID
D0R3EL
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.
NAD-dependent deacetylase sirtuin-1 (SIRT1)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for GSK184072. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of GSK184072 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [1], [2]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for GSK184072. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of GSK184072 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [2], [3]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for GSK184072. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of GSK184072 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [2], [4]
Protein virilizer homolog (VIRMA)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for GSK184072. The Protein virilizer homolog (VIRMA) has potential in affecting the response of GSK184072 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [2], [5]
References
Ref 1 SIRT1 Regulates N(6) -Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2-Dependent FTO SUMOylation. Hepatology. 2020 Dec;72(6):2029-2050. doi: 10.1002/hep.31222. Epub 2020 Oct 22.
Ref 2 SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
Ref 3 METTL14 aggravates podocyte injury and glomerulopathy progression through N(6)-methyladenosine-dependent downregulating of Sirt1. Cell Death Dis. 2021 Sep 27;12(10):881. doi: 10.1038/s41419-021-04156-y.
Ref 4 METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism. Biochem Biophys Res Commun. 2019 Oct 8;518(1):120-126. doi: 10.1016/j.bbrc.2019.08.018. Epub 2019 Aug 10.
Ref 5 m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner. Cell Death Discov. 2022 Feb 25;8(1):83. doi: 10.1038/s41420-022-00878-w.