fgf401

Description: Roblitinib (FGF-401) is a potent and highly selective inhibitor of human fibroblast growth factor receptor 4 (FGFR4) with an IC50 of 1.9 nM and with potential antineoplastic/anticancer activity. Upon administration, FGF401 binds to and inhibits the activity of FGFR4, which leads to an inhibition of tumor cell proliferation in FGFR4-overexpressing tumor cells. FGFR4 is a receptor tyrosine kinase upregulated in certain tumor cells and involved in tumor cell proliferation, differentiation, angiogenesis, and survival. FGF401 is being developed for hepatocellular carcinoma, currently in phase I/II clinical studies. In preclinical studies in mice and dogs, oral administration of FGF401 led to induction of Cyp7a1, elevation of its peripheral marker 7alpha-hydroxy-4-cholesten-3-one, increased BA pool size, decreased serum cholesterol and diarrhea in dogs. FGF401 was also associated with increases of serum aminotransferases, primarily alanine aminotransferase (ALT), in the absence of any observable adverse histopathological findings in the liver, or in any other organs.

References: Toxicol Sci. 2018 May 1; 163(1):265-278; WO2015059668A1.