Discovery of novel FABP1 inhibitors for the treatment of metabolic dysfunction-associated steatohepatitis and hepatic fibrosis.

ABSTRACT: The fatty acid-binding protein 1 (FABP1) has drawn increasing attention as a promising target for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). However, efforts to validate pharmacological effects of FABP1 are restricted by the lack of relevant inhibitors. Herein, we identified the lead compound 1 with potent inhibition on FABP1 through screening from our in-house library. Further comprehensive structure-activity relationship (SAR) study based on compound 1 resulted in the identification of the optimal compound 12 (IC₅₀ = 3.6 µM). Moreover, compound 12 exerted stronger efficacy on reducing hepatic lipid accumulation, inflammation and fibrosis than that of clinical candidate GFT505 in MASH models. In addition, compound 12 significantly inhibited fibros

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC12482055 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature