SR9238

Description: SR9238 is the first selective synthetic LXR (Liver X receptor) inverse antagonist with IC50s of 214 nM and 43 nM for LXRalpha and LXRbeta, respectively. SR9238 can effectively suppresses hepatic lipogenesis, inflammation, and hepatic lipid accumulation in a mouse model of non-alcoholic hepatosteatosis. SR9238 displays high potency for both LXRalpha and LXRbeta (40-200 nM IC50) and was designed to display liver specificity so as to avoid potential side effects due to suppression of LXR in the periphery. Unexpectedly, treatment of diet-induced obese mice with SR9238 suppressed plasma cholesterol levels. These data indicate that liver-selective LXR inverse agonists such as SR9238 may hold utility in the treatment of liver disease. Fatty liver, which often accompanies obesity and type 2 diabetes, frequently leads to a much more debilitating hepatic disease including non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Current pharmacological therapies lack conclusive efficacy and thus treatment options are limited. Novel therapeutics that suppress either hepatic lipogenesis and/or hepatic inflammation may be useful.

References: ACS Chem Biol. 2013 Mar 15; 8(3):559-67.