AEE788
Encyclopedia
AEE788is a novel 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.
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...
(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
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
, ErbB2, KDR
Kinase insert domain receptor
Kinase insert domain receptor also known as vascular endothelial growth factor receptor 2 is a VEGF receptor. KDR is the human gene encoding it. KDR has also been designated as CD309...
, 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 ERBB4 Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene. Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.... (HER-4) |
160 |
| KDR Kinase insert domain receptor Kinase insert domain receptor also known as vascular endothelial growth factor receptor 2 is a VEGF receptor. KDR is the human gene encoding it. KDR has also been designated as CD309... |
77 |
| Tek | 2100 |
| IGF1-R | >10000 |
| Ins-R | >10000 |
| PDGFR-beta | 320 |
| c-Met C-MET c-Met is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor . The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity... |
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 |