Elafibranor

923978-27-2

C22H24O4S

DMSO : >= 33 mg/mL (85.83 mM); H2O : < 0.1 mg/mL (insoluble)

Cell Cycle/DNA Damage

Elafibranor is a PPARalpha/delta agonist with EC₅₀s of 45 and 175 nM, respectively. IC50 & Target: EC50: 45 nM (PPAR-alpha), 175 nM (PPAR-delta)^[1] In Vitro: GFT505 is being developed as a dual PPAR-alpha/PPAR-delta agonist for the treatment of T2DM and non-alcoholic fatty liver disease. GFT505 has an active metabolite, GFT1007, and both have potent agonist activity for PPAR-alpha and to a lesser extent for PPAR-delta^[1]. In Vivo: GFT505 improves insulin sensitivity and early studies indicate it may be useful in non-alcoholic fatty liver disease which is being tested in a Phase IIb study^[1]. 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 insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation^[2]. 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 GFT505. GFT505 does not induce cardiac adverse effects of PPARgamma-activating agonists in monkeys^[3].