AEE788

AEE788 is an orally active inhibitor targeting EGFR and ErbB2 with IC₅₀ values of 2 and 6 nM, respectively^[1][2][3]. IC50 & Target:IC50: 2 nM (EGFR), 6 nM (ErbB2)^[1] In Vitro:AEE788 inhibits EGFR and VEGF receptor tyrosine kinases in the nM range (IC₅₀:EGFR 2 nm, ErbB2 6 nm, KDR 77 nm, and Flt-1 59 nm). In cells, growth factor-induced EGFR and ErbB2 phosphorylation is also efficiently inhibited (IC₅₀:11 and 220 nm, respectively). AEE788 demonstrates antiproliferative activity against a range of EGFR and ErbB2-overexpressing cell lines (including EGFRvIII-dependent lines) and inhibits the proliferation of epidermal growth factor- and VEGF-stimulated human umbilical vein endothelial cells^[1]. Treatment of cutaneous SCC cells with AEE788 leads to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis^[2]. In Vivo:AEE788 efficiently inhibits growth factor-induced EGFR and ErbB2 phosphorylation in tumors for >72 h. AEE788 also inhibits VEGF-induced angiogenesis in a murine implant model^[1]. In mice treated with AEE788, tumor growth is inhibited by 54% at 21 days after the start of treatment compared with control mice^[2].