Английская Википедия:AEE788
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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.[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.[2][3]
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 |
References