Benzoxazole Derivatives as Potent FXR and PPARα Dual Agonists With Anti-Fibrotic and Metabolic Regulatory Effects.

ABSTRACT: Fibrotic disease involves excessive fibrous connective tissue accumulation in organs, leading to dysfunction and irreversible damage. Metabolic alterations can sometimes contribute to fibrosis development. This study aimed to develop dual agonists for farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor alpha (PPARα), targeting anti-fibrosis and metabolic regulation. Benzoxazole derivatives were found to potently activate both FXR and PPARα in hepatocytes. Among them, MHY5396 showed the most potent effects with low EC₅₀ values. MHY5396 reduced lipid synthesis and enhanced beta-oxidation in hepatocytes, decreasing lipid accumulation. It also suppressed TGFβ-induced fibrosis in hepatic stellate cells. In a methionine/choline-deficient diet mouse model, MHY5396

SUBMITTER: Kim MJ 

PROVIDER: S-EPMC12554789 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature