GFT505 Derivatives Ameliorate Alcohol-Induced Hepatic Steatosis and Injury in Vivo and in Vitro

Abstract

Alcoholic fatty liver disease (AFLD) is a metabolic liver disorder induced by chronic alcohol consumption, characterized by hepatic steatosis, inflammation, and liver injury that may progress to cirrhosis or even hepatocellular carcinoma. Although the PPARα/δ dual agonist Elafibranor (GFT505) demonstrated metabolic improvement and anti-inflammatory effects in preclinical studies, it failed to achieve expected outcomes in clinical trials. In this study, we identified that its structurally optimized derivative 3a significantly attenuated hepatic lipid accumulation and ameliorated liver injury in both in vitro and in vivo AFLD models, exhibiting promising therapeutic potential. These findings suggest that compound 3a represents a viable drug candidate for AFLD treatment.

Keywords: AFLD; Hepatic lipid accumulation; GFT505 derivative