AEE788 (NVP-AEE788)

Catalog No.S1486

For research use only.

AEE788 (NVP-AEE788) is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM, less potent to VEGFR2/KDR, c-Abl, c-Src, and Flt-1, does not inhibit Ins-R, IGF-1R, PKCα and CDK1. Phase 1/2.

AEE788 (NVP-AEE788) Chemical Structure

CAS No. 497839-62-0

Selleck's AEE788 (NVP-AEE788) has been cited by 13 publications

Purity & Quality Control

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Biological Activity

Description AEE788 (NVP-AEE788) is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM, less potent to VEGFR2/KDR, c-Abl, c-Src, and Flt-1, does not inhibit Ins-R, IGF-1R, PKCα and CDK1. Phase 1/2.
Targets
EGFR [1]
(Cell-free assay)
HER2/ErbB2 [1]
(Cell-free assay)
c-Abl [1]
(Cell-free assay)
FLT1 [1]
(Cell-free assay)
c-Fms [1]
(Cell-free assay)
Click to View More Targets
2 nM 6 nM 52 nM 59 nM 60 nM
In vitro

AEE788 also inhibits KDR, c-abl, c-Src, and Flt-1 with IC50 of 50-80 nM. AEE788 is not sensitive to ErbB-4, PDGFR-β, Flt-3, Flt-4, RET, and c-Kit and has no inhibitory to Ins-R, IGF-1R, PKC-α, and PKA. AEE788 potently inhibits EGFR phosphorylation in A431 cells with IC50 of 11 nM. AEE788 also inhibits the phosphorylation of KDR in CHO cells and erbB2 in BT-474 cells, without any effects on PDGF-induced phosphorylation in A31 cells. AEE788 inhibits the proliferation of NCI-H596, MK, BT-474 and SK-BR-3 cells with IC50 of 78, 56, 49 and 381 nM, respectively. Otherwise, AEE788 has the additional property of inhibiting cellular proliferation driven by EGFR mutant including 32D/EGFR and 32D/EGFRvIII. AEE788 furtheralso inhibits both EGF- and VEGF-driven HUVEC proliferation with IC50 of 43 and 155 nM, respectively. [1] AEE788 inhibits the phosphorylation of EGFR, VEGFR2, Akt, and MAPK in human cutaneous SCC cell lines (Colo16, HaCaT, SRB1, and SRB12 cells), which leads to growth inhibition and induction of apoptosis. [2] AEE788 inhibits the phosphorylation of EGFR and Akt in HT29 cells at 0.2 to 1.0 μM. [3] AEE788 inhibits cell proliferation and prevents EGF- and neuregulin-induced HER1, HER2, and HER3 activation in medulloblastoma cell lines. AEE788 shows growth-suppressive activities in chemosensitive and chemoresistant medulloblastoma cells. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Huh7 MnXrR5l1d3SxeHnjbZR6KGG|c3H5 M{TWfWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJIhmeGG2b3PlcIx2dGG{IHPhdoNqdm:vYTDj[YxtKGyrbnWgLGh2cDdrLDDDR|UxRTJ5LkizJO6ddQ>? NIPGVW0yQDV5OUe4Ny=>
Jeko B cells M3i0[mZ2dmO2aX;uJIF{e2G7 NVnlVWYxOiCq MljmTY5pcWKrdHnvckBw\iCSSUPL[IVtfGFiaX6gbJVu[W5iSnXrc{BDKGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gRYt1KHCqb4PwbI9zgWyjdHnvckBi\nSncjCyJIhzeyxiSVO1NF0xNjBzNzFOwG0> NEnJVmMzPTVzNE[1PC=>
In vivo AEE788 produces a dose-dependent inhibition of tumor growth in NCI-H596 or DU145 xenograft models, with only minor body weight changes. AEE788 induces tumor regression by 57% at 50 mg/kg in the NeuT/erbB2 GeMag model. AEE788 potently inhibits EGF-induced EGFR phosphorylation in A431 tumors and erbB2 phosphorylation in GeMag tumors. AEE788 dose-dependently inhibited angiogenesis induced by VEGF and does not inhibit bFGF-induced angiogenesis. [1] AEE788 suppresses the growth of tumor volume by 54% in Colo16 xenografts at 50 mg/kg, which dues to the inhibition of phosphorylation of EGFR, VEGFR, Akt, and MAPK. [2] AEE788 (50 mg/kg) also inhibits growth of tumors in the cecum and peritoneum (>50%) and reduces the incidence of lymph node metastasis to 70% in HT29 cells implanted in the cecum of nude mice, without loss of body weight and gross evidence of neovascularization. AEE788 significantly lowers the expression levels of pEGFR and pVEGFR in HT29 cecal tumors and does not alter those of EGF, VEGF, EGFR, or VEGFR. Combined with CPT-11, AEE788 has significantly smaller tumors and complete inhibition of lymph node metastasis. [3] AEE788 inhibits the growth of Daoy, DaoyPt, and DaoyHER2 xenografts by 51%, 45%, and 72%, respectively. [4] AEE788 could promote LBH589-mediated generation of reactive oxygen species in K562 tumor cells, which in turn increase apoptosis. [5]

Protocol (from reference)

Kinase Assay:[1]
  • Protein Kinase Assays:

    The in vitro 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. With the exception of protein kinase C-α, cyclin-dependent kinase 1/cycB and protein kinase A are protamine sulfate (200 μg/mL), histone H1 (100 μg/mL), and the heptapeptide Leu-Arg-Arg-Ala-Ser-Leu-Gly (known as Kemptide Bachem) respectively and are used as peptide substrates. 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 (PDGFR-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 with 1.0% H3PO4 and once with ethanol. Dried membranes are counted after mounting in a Packard TopCount 96-well frame and with the addition of 10 μL/well of Microscint. IC50 values (±SE) are calculated by linear regression analysis of the percentage inhibition and are averages of at least three determinations.

Cell Research:[1]
  • Cell lines: T24, BT-474, SK-BR-3, and NCI-H596 cells
  • Concentrations: ~10 μM
  • Incubation Time: 4 or 6 days
  • Method: Methylene Blue Cell Proliferation Assay.Cells are seeded at 1.5 × 103 cells/well into 96-well microtiter plates and incubated overnight at 37 °C, 5% v/v CO2 and 80% relative humidity. AEE788 dilutions are added on day 1, with the highest concentration being 10 μM. After incubation of the cell plates for an additional 4 (T24) or 6 (BT-474, SK-BR-3, and NCI-H596) days, cells are fixed with 3.3% v/v glutaraldehyde, washed with water, and stained with 0.05% w/v methylene blue. After washing, the dye is eluted with 3% HCl and the absorbance measured at 665 nm with a SpectraMax 340 spectrophotometer. IC50 values are determined by mathematical curve-fitting and are defined as the drug concentration leading to 50% inhibition of net cell mass increase compared with untreated control cultures.
Animal Research:[1]
  • Animal Models: NCI-H596, DU145, A431, B16 and oncogenic NeuT-transfected HC11 cells in female BALB/c nu/nu (nude) mice
  • Dosages: 50 mg/kg
  • Administration: Dosed orally

Solubility (25°C)

In vitro

DMSO 88 mg/mL
(199.73 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 440.58
Formula

C27H32N6

CAS No. 497839-62-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4NC(C)C5=CC=CC=C5

In vivo Formulation Calculator (Clear solution)

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00107237 Completed Drug: AEE788|Drug: everolimus Brain and Central Nervous System Tumors Novartis Pharmaceuticals|Novartis October 2003 Phase 1|Phase 2
NCT00118456 Completed Drug: AEE788 Cancer Novartis Pharmaceuticals|Novartis July 2003 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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