Alofanib

Alofanib is a novel selective allosteric inhibitor of fibroblast growth factor receptor 2 (FGFR2) tyrosine kinase. It inhibits phosphorylation of FGF receptor substrate 2α (FRS2α) with IC₅₀ values of 7 nM and 9 nM in cancer cells expressing different FGFR2 isoforms. It inhibits FGF-mediated proliferation in a panel of four cell lines representing tumor types such as triple-negative breast cancer, melanoma, and ovarian cancer with 50% growth inhibition (GI₅₀) values of 16 nM-370 nM. It inhibits the proliferation and migration of human and mouse endothelial cells. It ablates experimental FGF-induced angiogenesis in vivo. Oral administration of alofanib shows potent antitumor activity in a FGFR-driven human tumor xenograft model.