AEE788[1] is 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.[2] 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.[3][4]
Here is 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
|
References
- ^ Biological Activity of AEE788
- ^ 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. (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. PMID 15256466. CS1 maint: multiple names: authors list (link)
- ^ Juengel E, Engler J, Natsheh I, Jones J, Mickuckyte A, Hudak L, Jonas D, Blaheta RA. (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). PMID 19473483. CS1 maint: multiple names: authors list (link)
- ^ Meco D, Servidei T, Zannoni GF, Martinelli E, Prisco MG, de Waure C, Riccardi R. (2010). "Dual Inhibitor AEE788 Reduces Tumor Growth in Preclinical Models of Medulloblastoma". Transl Oncol. 3 (5): 326–35. PMID 20885895. CS1 maint: multiple names: authors list (link)