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AEE788 (NVP-AEE788) Catalog No.GC11892

EGFR/HER-2/VEGFR inhibitor

Size Price Stock Qty
10mM (in 1mL DMSO)
$96.00
In stock
5mg
$64.00
In stock
10mg
$113.00
In stock
25mg
$259.00
In stock
50mg
$416.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & SDS

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Protocol

Kinase experiment:

The invitro kinase assays are performed in 96-well plates (30 μL) at ambient temperature for 15–45 min using the recombinant glutathione S-transferase-fused kinase domains (4–100 ng, depending on specific activity). [γ33P]ATP is used as phosphate donor and polyGluTyr-(4:1) peptide as acceptor. Assays are optimized for each kinase using the following ATP concentrations: 1.0 μM (c-Kit, c-Met, c-Fms, c-Raf-1, and RET), 2.0 μM (EGFR, ErbB2, ErbB3, and ErbB4), 5.0 μM (c-Abl), 8.0 μM (Flt-1, Flt-3, Flt-4, Flk, KDR, FGFR-1, and Tek), 10.0 μM (PDGF receptor-β, protein kinase C-α, and cyclin-dependent kinase 1), and 20.0 μM (c-Src and protein kinase A). The reaction is terminated by the addition of 20 μL 125 mM EDTA. Thirty μL (c-Abl, c-Src, insulin-like growth factor-1R, RET-Men2A, and RET-Men2B) or 40 μL (all other kinases) of the reaction mixture is transferred onto Immobilon-polyvinylidene difluoride membrane, presoaked with 0.5% H3PO4 and mounted on a vacuum manifold. Vacuum is then applied and each well rinsed with 200 μL 0.5% H3PO4. Membranes are removed and washed four times. Dried membranes are counted. IC50 are calculated by linear regression analysis of the percentage inhibition and are averages of at least three determinations[1].

Cell experiment:

AEE788 is dissolved in 90% polyethylene glycol 300 plus 10% 1-methyl-2-pyrrolidinone to a concentration of 6.25 mg/mL. Tumor cells are seeded into 96-well plates in complete medium and allowed to attach for 24 hours. The cultures are re-fed with medium with 2% serum. After 24 hours, cells are treated with different concentrations (0-2 μM) of AEE788 (negative control with DMSO alone) for 72 hours. After a 2-hour incubation in medium containing 0.42 mg/mL MTT, the cells are lysed in 100 μL DMSO. The conversion of MTT to formazan is measured at an absorbance of 570 nm[2]

Animal experiment:

Mice: AEE788 is diluted in DMSO and diluted in the optimal medium. BALB/c mice bearing s.c. A-431 squamous tumors (3 animals/group) or HC11-NeuT-driven breast tumors (2 animals/group) are dosed orally with 30 mg/kg of AEE788 or vehicle once daily for 5 days. At different time points after the end of compound treatment and before sacrificing the animals the mice are given i.v. 500 μg EGF/kg body weight or 0.2 ml 0.9% w/v NaCl as vehicle control. Five min after EGF administration, the mice are sacrificed, tumors are removed[1].

References:

[1]. Traxler P, et al. 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. 2004 Jul 15;64(14):4931-4941.
[2]. Park et al. AEE788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice. Clin Cancer Res. 2005 Mar 1;11(5):1963-1973.

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Chemical Properties

Cas No. 497839-62-0 SDF
Chemical Name 6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
Canonical SMILES CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4NC(C)C5=CC=CC=C5
Formula C27H32N6 M.Wt 440.58
Solubility ≥22.05mg/mL in DMSO, ≥14.4 mg/mL in EtOH with ultrasonic, <2.32 mg/mL in H2O Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Background

AEE788 is a potent inhibitor of EGFR and HER2 (IC50=2 nM and 6 nM)

EGFR (epidermal growth factor receptor) is a cell-surface receptor tyrosine kinase. The receptor activation leads to dimerization and tyrosine autophosphorylation. It induces a cascade of downstream cellular responses such as modification in gene expression, cell proliferation and cytoskeletal rearrangement etc.

In HCT 15 colon cancer cells, AEE788 potentiated celecoxib-mediated blockage of proliferation and angiogenesis [1]. In various cell line with EGFR and HER2-overexpressing, AEE788 exhibited antiproliferative activity [3]. AEE788 also inhibited cell proliferation (IC50=1.7-3.8 µM) and prevented epidermal growth factor and neuregulin-induced activation of HER1, HER2, and HER3 in vitro [5].

Comparing with the control mice, AEE788 treated mice showed 54% inhibited tumor growth in 21 days after the initiation of the treatment [2]. In ZR75.1 A3 xenograft mice, letrozole combined with AEE788 had a prominently greater tumor growth inhibition compared with letrozole treatment alone [4].

References:
[1] Venkatesan P, Bhutia SK, Singh AK et al.  AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells. Life Sci. 2012 Oct 22;91(15-16):789-99.
[2] Park YW, Younes MN, Jasser SA et al.  AEE788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice. Clin Cancer Res. 2005 Mar 1;11(5):1963-73.
[3] Traxler P, Allegrini PR, Brandt R et al.  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. 2004 Jul 15;64(14):4931-41.
[4] Evans AH, Pancholi S, Farmer I et al.  EGFR/HER2 inhibitor AEE788 increases ER-mediated transcription in HER2/ER-positive breast cancer cells but functions synergistically with endocrine therapy.  Br J Cancer. 2010 Apr 13;102(8):1235-43.
[5] Meco D, Servidei T, Zannoni GF et al.  Dual Inhibitor AEE788 Reduces Tumor Growth in Preclinical Models of Medulloblastoma. Transl Oncol. 2010 Oct 1;3(5):326-35.