Biochem/physiol Actions
SR9238 is liver selective LXR inverse agonist with high potency for both LXRα and LXRβ with an IC50 of 214 nM for LXRα and 43 nM for LXRβ. Metabolic syndrome is often accompanied by liver problems, such as fatty liver (nonalcoholic hepatosteatosis), associated with increased lipogenesis. Liver X receptors α and β (LXRα and LXRβ) are known to induce lipogenesis by increasing transcription of lipogenic enzyme genes, so it was hoped LXR antagonists might be of use in fatty liver. In a mouse model of nonalcoholic hepatosteatosis, SR9238 reduced the expression of lipogenic genes, and suppressed hepatic lipogenesis, inflammation and hepatic lipid accumulation. It was also effective in reduction of hepatic fibrosis in another study. Additionally in diet induced obese mice, SR9238 suppressed plasma cholesterol levels.
