ELOVL6 inhibitor Compound B is a potent and selective ELOVL6 inhibitor with IC50 of 85 and 38 nM for human and mouse ELOVL6, respectively.
Compound B is about 10-fold greater than that of Compound A.
Compound B displays >60-fold selectivity over the other ELOVL family enzymes (ELOVL1, 2, 3, and 5).
Compound B shows the mode-of-action of an ELOVL6 inhibitor in a non-competitive manner for malonyl-CoA and in an un-competitive manner for palmitoyl CoA.
Compound B effectively inhibits ELOVL6 activity in the liver.
Compound B shows significant reduction in hepatic fatty acid composition in model animals, diet-induced obesity (DIO) and KKAy mice.
