TGF-β Pathway Inhibition by Compound X Reduces Hepatic Fibrosis in Murine Models

Abstract

Hepatic fibrosis represents a major clinical challenge with limited therapeutic options. Here we demonstrate that Compound X, a novel small-molecule inhibitor of TGF-β receptor kinase activity, significantly reduces fibrosis progression in multiple murine models. Using bleomycin-induced and carbon tetrachloride models, we show that daily oral administration of Compound X at 10mg/kg reduces collagen deposition by 67% and α-SMA expression by 54% after 8 weeks of treatment. Mechanistically, Compound X inhibits TGF-β receptor phosphorylation with an IC50 of 2.3nM, blocking downstream Smad2/3 activation. No significant hepatotoxicity was observed at therapeutic doses. These findings support further clinical development of Compound X for fibrotic liver diseases.

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