Background:

ZD6474 is a dual inhibitor of VEGFR-2 and EGFR with IC50 values of 40 nM and 500 nM, respectively [1].

ZD6474 showed potent inhibition activities against recombinant VEGFR-2 and EGFR in the in vitro assays. The inhibition of VEGFR-2 was 2.7-fold more potent than that of VEGFR-3 (Flt-4) kinase and 40-fold more potent than that of VEGFR-1. In human umbilical vein endothelial cells, treatment of ZD6474 resulted in significant inhibition of cell proliferation stimulated by VEGF and EGF with IC50 values of 60 and 170 nM, respectively. Through inhibiting the kinase activity of EGFR, ZD6474 can inhibit cell growth of various cancer cell lines, including lung, ovarian, breast and colon cancers. Besides that, ZD6474 administration inhibited tumor growth in a dose-dependent manner in many tumor xenograft models.

参考文献:
[1] Ryan A J, Wedge S R. ZD6474–a novel inhibitor of VEGFR and EGFR tyrosine kinase activity[J]. British journal of cancer, 2005, 92: S6-S13.