Roblitinib

Roblitinib is a reversible-covalent inhibitor of fibroblast growth factor receptor 4 (FGFR4) tyrosine kinase. It shows 1000-fold selectivity for FGFR4 over FGFR1/2/3 and other kinases, with an IC₅₀ value of 1.9 nM against FGFR4. It shows potent antitumor activity in mice bearing Hepatocellular carcinoma (HCC) tumor xenografts and patient-derived tumor xenograft PDX models. FGF401 has entered phase I/II clinical trials to evaluate its safety and efficacy in HCC and other solid tumors. It leads to upregulation of bile acid synthesis and a subsequent increase in ALT expression in preclinical studies, which can be prevented by combination with the bile acid sequestrant cholestyramine.