SR9238

SR9238 is a liver-selective inverse agonist of the Liver X Receptors (LXRα and LXRβ). Developed by researchers at Scripps Research, it was designed to treat metabolic disorders such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Unlike LXR agonists, which promote lipogenesis and can cause hepatic steatosis, SR9238 suppresses the expression of lipogenic genes, including SREBP-1c and fatty acid synthase (FASN), thereby reducing liver fat content, inflammation, and fibrosis in animal models. Its liver selectivity is intended to avoid potential adverse effects in other tissues, such as the brain or peripheral macrophages. Recent research has also explored its role in oncology, specifically in pancreatic cancer, where it has been observed to stabilize LXR protein levels, though it appears insufficient to inhibit cell proliferation compared to newer LXR-targeting degraders.