Elafibranor

A nove, potent dual PPAR α/δ agonist with EC50 of 45 and 175 nM, respectively; demonstrates liver-protective effects on steatosis, inflammation, and fibrosis in animal models of NAFLD/NASH and liver fibrosis; significantly reduces fasting plasma triglycerides and increases HDL cholesterol, also reduces γ glutamyl transferase levels.Diabetes Phase 3 Clinical (In Vitro) :Elafibranor (GFT505) is being developed as a dual PPAR-α/PPAR-δ agonist for the treatment of T2DM and non-alcoholic fatty liver disease. Elafibranor has an active metabolite, GFT1007, and both have potent agonist activity for PPAR-α and to a lesser extent for PPAR-δ. (In Vivo) :Elafibranor is well tolerated and does not cause weight gain or cardiac events, but does produce a mild, reversible increase in serum creatinine. Elafibranor improves glucose homeostasis, and lipid metabolism and reduces inflammation. Elafibranor (GFT505) treatment improves glucose control and plasma lipids in diabetic db/db mice. A significant dose-dependent reduction of hepatic expression of the key gluconeogenic enzymes glucose 6-phosphatase (G6Pase), PEPCK, and fructose 1,6-bisphosphatase 1 (FBP1) is observed with Elafibranor. Elafibranor does not induce cardiac adverse effects of PPARγ-activating agonists in monkeys.