Elafibranor CAS:923978-27-2

GFT505 is a new dual agonist of the PPARα and PPARδ isoforms, which improves lipid and glucose metabolism in type 2 diabete mellito (T2DM) and exerts hepatoprotective effects in mouse models of nonalcoholic fatty liver disease (NAFLD).

Elafibranor (GFT505) is an experimental medication that is being studied and developed by Genfit for the treatment of cardiometabolic diseases including diabetes, insulin resistance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD).

Elafibranor is a dual PPARα/δ agonist.

Elafibranor is an agonist of the peroxisome proliferator-activated receptors (PPAR) α and δ.1 It increases HDL secretion and expression of the lipid-related genes ABCA1, PLIN2, and ABHD5 in Caco-2/TC7 cells in a PPARα-dependent manner. Elafibranor (10 mg/kg) decreases levels of plasma triglycerides and total cholesterol while increasing plasma HDL and expression of Acox1, a PPARα target gene, in the liver of ApoE2-KI wild-type, but not PPARα knockout, mice fed a Western diet. Tuttavia, PPARα knockout mice exhibit a decrease in plasma total and non-HDL cholesterol levels, indicating PPARδ has a role in these functions. Elafibranor (30 mg/kg) reduces diet-induced macro- and micro-steatosis in a PPARα-deficient mouse model of non-alcoholic steatohepatitis.2 It also reduces cholesterol and triglyceride accumulation as well as macrovesicular steatosis in the liver of insulin-resistant db/db mice fed the methionine-choline deficient (MCD) diet. Formulations containing elafibranor are under clinical investigation for the treatment of non-alcoholic steatohepatitis.