Elafibranor

Elafibranor (GFT505) is a PPARα/δ agonist with EC₅₀s of 45 and 175 nM, respectively. Elafibranor can be used for the study of primary biliary cholangitis^[1]. IC50 & Target:EC50: 45 nM (PPAR-α), 175 nM (PPAR-δ)^[1] In Vitro:Elafibranor (GFT505) is being developed as a dual PPAR-α/PPAR-δ agonist for the inhibition 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^[1]. 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^[2]. 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^[3].