An allosteric inhibitor of FGFR2
Alofanib is an allosteric inhibitor of FGFR2.1,2 It inhibits FGF2-induced phosphorylation of FGFR substrate 2 (FRS2α) in KATO III gastric carcinoma cells (IC50 = <10 nM).2 Alofanib inhibits the growth of SKOV3 ovarian and Hs 578T breast cancer cells (GI50s = 370 and 210 nM, respectively). It inhibits proliferation of human umbilical vein endothelial cells (HUVECs) induced by basic FGF (bFGF; IC50 = 11 nM) and tube formation of SVEC4-10 endothelial cells when used at a concentration of 50 nM.1 It also inhibits migration of SVEC4-10 cells in a wound healing assay. Alofanib (50 mg/kg) decreases the number of microvessels in tumor tissue by 50% in a SKOV3 ovarian serous carcinoma mouse model. It reduces tumor growth in mouse xenograft models when administered at a dose of 30 mg/kg per day, and the degree of tumor volume reduction positively correlates with the expression level of FGFR22
1.Khochenkov, D.A., Solomko, E.S., Peretolchina, N.M., et al.Antiangiogenic activity of alofanib, an allosteric inhibitor of fibroblast growth factor receptor 2Bull. Exp. Biol. Med.160(1)84-87(2015) 2.Tsimafeyeu, I., Ludes-Meyers, J., Stepanova, E., et al.Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour modelsEur. J. Cancer6120-28(2016)
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