AEE788

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]

AEE788
Identifiers
IUPAC name
  • 6-[4-[(4-Ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H32N6
Molar mass440.595 g·mol−1
3D model (JSmol)
SMILES
  • CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4N[C@H](C)C5=CC=CC=C5
InChI
  • 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 Y
  • Key:OONFNUWBHFSNBT-HXUWFJFHSA-N Y
 NY (what is this?)  (verify)

The IC50 value of AEE788 against of different kinases

KinaseIC50(nM)
EGFR ICD2
ErbB2(HER-2)6
ErbB4 (HER-4)160
KDR77
Tek2100
IGF1-R>10000
Ins-R>10000
PDGFR-beta320
c-Met2900
c-Abl52
c-Src61
c-Kit790
RET740
c-Fms60
Flt-159
Flt-3730
Flt-4330
Cdk1/Cyc.B8000
PKC-alpha>10000
c-Raf-12800
PKA>10000

The data of antiproliferative activity of AEE788

Cell lineIC50(nM)
NCI-H59678
MK56
BT-47449
SK-BR-3381
32D/EGFR300
32D/EGFRvIII10
MCF-72500
MCF-7/EGFRvIII<5000
T244526

References

  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.
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