Seladelpar

Seladelpar has been used as a PPARδ agonist to study its role in reducing bile acid synthesis in hepatocytes.

Seladelpar (MBX-8025) is an orally active, potent and selective Peroxisome proliferator–activated receptor delta (PPAR-δ) agonist (EC50 = 2 nM post 24h treatment using HEK293 PPARβ/δ reporter cells) with >750- and >2500-fold higher potency over that of PPAR-α and PPAR-γ, respectively. Seladelpar reduces ethanol-induced liver disease by restoring gut barrier function and bile acid homeostasis in mice in vivo (10 mg/kg/d via liquid diet). Seladelpar plays a significant role in regulating bile acid metabolism and inflammation. By activating PPARδ, seladelpar promotes fatty acid oxidation and reduces lipid accumulation in the liver, which is predominantly observed in primary biliary cholangitis (PBC) and non-alcoholic steatohepatitis (NASH). PPARδ activation also results in the downregulation of bile acid synthesis by reducing the expression of cholesterol 7 alpha-hydroxylase (CYP7A1), a key enzyme in bile acid synthesis. Seladelpar also enhances the signaling of fibroblast growth factor 21 (FGF21), contributing to its anti-inflammatory effects.