SR9238 is a synthetic agonist of liver X receptor inverse (IC50s: 214 nM and 43 nM for LXRα and LXRβ, respectively).

LXRβ:43 nM, LXRα:214 nM

SR9238 effectively suppresses transcription from a fatty acid synthase promoter-driven luciferase reporter. SR9238 is a synthetic LXR inverse agonist (IC50s: 214 nM and 43 nM for LXRα and LXRβ, respectively). SR9238-induced recruitment of CoRNR box peptides is dose-dependent for both LXRα and LXRβ. It is found that SR9238 induces increased interaction of CoRNR box peptides derived from NCoR with both LXRα and LXRβ while causing decreased interaction with a coactivator NR box peptide derived from TRAP220. HepG2 cells treated with SR9238 cause a significant decrease in Fasn and Srebp1c mRNA expression[1].

SR9238 treatment inhibits diet-induced hepatosteatosis, hepatic inflammation, and hepatocellular injury. SR9238 is also detected in the intestine with either i.p. or oral administration. Approximately SR9238 (6 μM) is detected in the liver 2h after the injection of SR9238, but no compound is detected in the plasma. SR9238-treated mice show greatly reduced lipid content in the liver. Both Tnfa and Il1b expression are substantially reduced (~80% and >95%, respectively) in the SR9238-treated mice when compared to the vehicle-treated mice. SR9238-treated DIO mice display a considerably lower intensity of F4/80 staining versus vehicle-treated DIO mice consistent with a beneficial effect of SR9238 on non-alcoholic steatohepatitis. SR9238 treatment does not alter body weight or percent body fat composition relative to vehicle-treated animals during the experiment [1].