AEE788 can potently inhibit EGFR, ErbB2, KDR, and Flt-1with IC50 of 2 nM, 6 nM, 77 nM and 59 nM, respectively.
In vivo
AEE788 inhibits EGFR and ErbB2 phosphorylation in cells with IC50 of 11 nM and 22 nM, respectively. AEE788 demonstrates antiproliferative activity against a range of EGFR and ErbB2-overexpressing cell lines (including EGFRvIII-dependent lines) and inhibited the proliferation of epidermal growth factor- and VEGF-stimulated human umbilical vein endothelial cells. AEE788 shows potent antitumor activity in a number of animal models of cancer, including tumors that overexpress EGFR and or ErbB2. AEE788 was able to inhibit the proliferation and induce apoptosis of ATC cell lines in vitro, and anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies.[2]Treatment of cutaneous SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis.[3]