AEE788

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AEE788
AEE788.svg
Systematic (IUPAC) name
6-[4-[(4-Ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
Clinical data
Legal status ?
Identifiers
CAS number 497839-62-0 N
ATC code ?
PubChem CID 10297043
ChemSpider 8472511 YesY
ChEMBL CHEMBL587723 YesY
Chemical data
Formula C27H32N6 
Mol. mass 440.58318 g/mol
 N (what is this?)  (verify)

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.[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[edit]

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[edit]

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[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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.