GSK837149A

GSK837149A is a selective and reversible inhibitor of fatty acid synthase (FAS) [1].

Fatty acids are essential for all the living cells and have a diversity of biological functions. Fatty acids are fundamental aliphatic acids served as energy production and storage, cellular structure and as intermediates in the biosynthesis of hormones and other biologically important molecules. In cells, fatty acids provide structural integrity to cellular membranes and cell walls. Fatty acids have been also involved in the transmission of cellular signals and can be used to modify proteins during post-translational processing. Fatty acid synthase has been involved in catalyzing the formation of long-chain fatty acids from acetyl-CoA and malonyl-CoA in the presence of NADPH [1].

GSK837149A inhibited FAS in a reversible manner, with a Ki value of ~30 nm. GSK837149A possibly bound to the enzyme–ketoacyl-ACP complex [1]. GSK837149A selectively and reversibly inhibited the activity of FAS with the pIC50 of 7.8 [1]. GSK837149A functioned by inhibiting the β-ketoacyl reductase activity of FAS [1].

Reference:
[1] Vázquez M J, Leavens W, Liu R, et al.  Discovery of GSK837149A, an inhibitor of human fatty acid synthase targeting the β‐ketoacyl reductase reaction[J]. FEBS journal, 2008, 275(7): 1556-1567.