Elafibranor | PPARalpha/delta agonist

Elafibranor (923978-27-2) is a dual PPARα/δ agonist (EC₅₀ PPARα = 10-20 nM; PPARδ = 100-150 nM).¹ It was able to decrease plasma triglycerides levels¹, increase HDL cholesterol levels in human studies¹, and improve hepatic and peripheral insulin sensitivity². Elafibranor’s antidiabetic effects in db/db were without the adverse cardiac effects seen in PPARγ agonism.³ Elafibranor has also been shown to have therapeutic promise in the treatment of nonalcoholic steatohepatitis (NASH).^4-6

References/Citations:

1) Cariou et al. (2011) Effects of the New Dual PPARα/δ Agonist GFT505 on Lipid and Glucose Homeostasis in Abdominally Obese Patients With Combined Dyslipidemia or Impaired Glucose Metabolism; Diabetes Care 34 2008
2) Cariou et al. (2013) Dual peroxisome proliferator receptor α/δ agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects; Diabetes Care 36 2923
3) Hanf et al. (2014) The dual peroxisome proliferator-activated alpha/delta agonist GFT505 exerts anti-diabetic effects in db/db mice without peroxisome proliferator-activated receptor gamma-associated adverse cardiac effects.; Diab. Vasc. Dis. Res. 11 440
4) Staels et al. (2013) Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha-delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis; Hepatology 58 1941
5) Ratziu et al. (2016) Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening.; Gastroenterology. 39 2951
6) Boeckmans et al. (2019) Elafibranor restricts lipogenic and inflammatory responses in a human skin stem cell-derived model of NASH.; Pharmacol. Res. 114 377