Biological Activity:
The activity of EXEL-7647 (XL647), a novel spectrum-selective kinase inhibitor with potent activity against the EGF and vascular endothelial growth factor receptor tyrosine kinase families, against both wild-type (WT) and mutant EGFR in vitro and in vivo[1,2] .EXEL-7647 potently inhibits the EGFR and ErbB2 with IC50 0.3 and 16 nM respectively[2] .EXEL-7647 inhibits cellular proliferation and EGFR pathway activation in the erlotinib-resistant H1975 cell line that harbors a double mutation (L858R and T790M) in the EGFR gene. EXEL-7647 substantially inhibited the growth of H1975 xenograft tumors and reduced both tumor EGFR signaling and tumor vessel density. Additionally, EXEL-7647 substantially inhibited the growth and vascularization of MDAMB-231 xenografts, a model which is more reliant on signaling through vascular endothelial growth factor receptors[2] .References on XL647[1] Clin Cancer Res., 2008 Apr 15, 14(8):2465-75.[2] Clin Cancer Res., 2007 Jun 15, 13(12):3713-23