In Vivo Study of GFT-505 Selenium-Substituted Derivatives for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis

Metabolic dysfunction-associated steatohepatitis(MASH) is a common liver disease worldwide and can develop into liver cirrhosis and liver cancer.Current treatment is limited, and the only drug Rezdiffra has limited effects.GFT-505 performed well as a PPAR agonist in stage II, but not as expected in stage III.We replaced the sulfur atom of GFT-505 with selenium to obtain compound 4c.Study evaluating the effect of 4c on the MASH mouse model induced by MCD.The results showed that 4c improved MASH through multi-target synergy and reduced TG and ALT better than GFT-505.This finding provides a theoretical basis and new ideas for the development of novel multi-target anti-MASH drugs.