AEE788
AEE788|
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| Systematic (IUPAC) name |
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6-[4-[(4-Ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine |
| Identifiers |
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| CAS Number |
497839-62-0  N |
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| PubChem |
CID 10297043 |
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| IUPHAR/BPS |
7643 |
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| ChemSpider |
8472511  Y |
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| ChEMBL |
CHEMBL587723 Y |
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| Chemical data |
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| Formula |
C27H32N6 |
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| Molar mass |
440.58318 g/mol |
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CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4N[C@H](C)C5=CC=CC=C5
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InChI=1S/C27H32N6/c1-3-32-13-15-33(16-14-32)18-21-9-11-23(12-10-21)25-17-24-26(28-19-29-27(24)31-25)30-20(2)22-7-5-4-6-8-22/h4-12,17,19-20H,3,13-16,18H2,1-2H3,(H2,28,29,30,31)/t20-/m1/s1 YKey:OONFNUWBHFSNBT-HXUWFJFHSA-N Y
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| NY (what is this?) (verify) |
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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
- ↑ Traxler P, Allegrini PR, Brandt R, Brueggen J, Cozens R, Fabbro D, Grosios K, Lane HA, McSheehy P, Mestan J, Meyer T, Tang C, Wartmann M, Wood J, Caravatti G. (Jul 2004). "AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity". Cancer Res. 64 (14): 4931–41. doi:10.1158/0008-5472.CAN-03-3681. PMID 15256466.
- ↑ Juengel E, Engler J, Natsheh I, Jones J, Mickuckyte A, Hudak L, Jonas D, Blaheta RA. (May 2009). "Combining the receptor tyrosine kinase inhibitor AEE788 and the mammalian target of rapamycin (mTOR) inhibitor RAD001 strongly inhibits adhesion and growth of renal cell carcinoma cells". BMC Cancer. 9 (161): 161. doi:10.1186/1471-2407-9-161. PMC: 2693528. PMID 19473483.
- ↑ Meco D, Servidei T, Zannoni GF, Martinelli E, Prisco MG, de Waure C, Riccardi R. (Oct 2010). "Dual Inhibitor AEE788 Reduces Tumor Growth in Preclinical Models of Medulloblastoma.". Transl Oncol. 3 (5): 326–35. PMC: 2935636. PMID 20885895.
