AEE788 is a multitargeted human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2 receptor family tyrosine kinases inhibitor with IC50 of 2, 6, 77, 59 nM for EGFR, ErbB2, KDR, and Flt-1. In cells, growth factor-induced EGFR and ErbB2 phosphorylation was also efficiently inhibited with IC50s of 11 and 220 nM, respectively. It efficiently inhibited growth factor-induced EGFR and ErbB2 phosphorylation in tumors for >72 h, a phenomenon correlating with the antitumor efficacy of intermittent treatment schedules. It also inhibits VEGF-induced angiogenesis in a murine implant model. It has potential as an anticancer agent targeting deregulated tumor cell proliferation as well as angiogenic parameters.
The IC50 value of AEE788 against of different kinases Kinase IC50(nM) EGFR ICD 2 ErbB2(HER-2) 6 ErbB4 (HER-4) 160 KDR 77 Tek 2100 IGF1-R >10000 Ins-R >10000 PDGFR-beta 320 c-Met 2900 c-Abl 52 c-Src 61 c-Kit 790 RET 740 c-Fms 60 Flt-1 59 Flt-3 730 Flt-4 330 Cdk1/Cyc.B 8000 PKC-alpha >10000 c-Raf-1 2800 PKA >10000
The data of antiproliferative activity of AEE788 Cell line IC50(nM) NCI-H596 78 MK 56 BT-474 49 SK-BR-3 381 32D/EGFR 300 32D/EGFRvIII 10 MCF-7 2500 MCF-7/EGFRvIII <5000 T24 4526
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