Description
InformationAlofanib (RPT835) Alofanib (RPT835) is a novel selective allosteric inhibitor of FGFR2 and has a dramatic inhibitory effect with IC50 <10 nM on FGF2-induced phoshphorylation of FRS2a in KATO III cells. It has no direct effect on FGF2-dependent FGFR1 and FGFR3 phosphorylation levels in either cell lines and no effects on FGF2-FGFR2 binding.TargetsFGFR2 (Cell-free assay)In vitroAlofanib induces mainly apoptosis with cleavage of caspase 3, PARP and Bcl-2 in SKOV3 cell line. Cytotoxic effect of compound on ovarian cancer cells is low. Alofanib inhibits phosphorylation of FRS2α with the IC50 values of 7 and 9 nmol/l in cancer cells expressing different FGFR2 isoforms. In a panel of four cell lines representing several tumour types (triple-negative breast cancer,melanoma, and ovarian cancer), alofanib inhibits FGF-mediated proliferation with 50% growth inhibition (GI50) values of 16-370 nmol/l. Alofanib dose dependently inhibits the proliferation and migration of human and mouse endothelial cells (GI50: 11-58 nmol/l) compared with brivanib and bevacizumab.In vivoIntravenous alofanib significantly in dose-dependent manner potentiated the efficiency of the combination of paclitaxel and carboplatin. Alofanib suppresses angiogenesis in ovarian cancer mouse model. In a FGFR-driven human tumour xenograft model, oral administration of alofanib is well tolerated and results in potent antitumour activity.Cell Research(from reference)Cell lines：SKOV3 cells Concentrations：0-1 µM Incubation Time：72 h