AEE788

SKU: orb1306446

Description

AEE788 (NVP-AEE 788) is a small molecule inhibitor investigated in preclinical cancer research, particularly for glioblastoma and CNS tumors. It functions by targeting EGFR and VEGFR tyrosine kinases, and its antitumor efficacy has been studied in both in vitro cell assays and in vivo animal models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 497839-62-0
• MW: 440.58
• Purity: 98.00%
• Formula: C₂₇H₃₂N₆
• SMILES: CCN1CCN(Cc2ccc(cc2)-c2cc3c(N[C@H](C)c4ccccc4)ncnc3[nH]2)CC1
• Target: Apoptosis,Bcr-Abl,c-Fms,FLT,EGFR
• Solubility: DMSO:82 mg/mL (186.12 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.49 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  EGFR:2 nM|HER2/ErbB2:6 nM|FLK1:59 nM|c-Fms:60 nM|c-ABL:52 nM
• In Vivo:
  AEE788 inhibits the phosphorylation of EGFR and Akt in HT29 cells at concentrations of 0.2-1.0 μM. It also suppresses phosphorylation of EGFR, VEGFR2, Akt, and MAPK in human skin SCC cell lines (Colo16, HaCaT, SRB1, and SRB12), resulting in growth inhibition and apoptosis induction. AEE788 effectively inhibits EGFR phosphorylation in A431 cells, with an IC50 of 11 nM. Additionally, it impedes the phosphorylation of KDR in CHO cells and erbB2 in BT-474 cells, while having no effect on PDGF-induced phosphorylation in A31 cells. AEE788 targets medulloblastoma cell lines, inhibiting cell proliferation and the activation of HER1, HER2, and HER3 induced by EGF and neuregulin. It reduces cell proliferation in NCI-H596, MK, BT-474, and SK-BR-3 cells, with IC50 values of 78, 56, 49, and 381 nM, respectively. AEE788 also hinders EGF and VEGF-promoted proliferation of human umbilical vein endothelial cells, with IC50 values of 43 and 155 nM, respectively.
• In Vitro:
  AEE788, administered at a dosage of 50 mg/kg, effectively inhibits the growth (>50%) of cecal and peritoneal tumors and reduces the lymph node metastasis rate of HT29 cells implanted in the cecum of nude mice to 70%, without affecting the body weight. This compound causes a 57% tumor regression in the NeuT/ErbB2 GeMag model and inhibits EGFR phosphorylation induced by EGF in A431 tumors and erbB2 phosphorylation in GeMag tumors. In NCI-H596 or DU145 xenograft models, AEE788 demonstrates dose-dependent tumor growth inhibition with minimal weight changes. It enhances apoptosis by promoting the production of reactive oxygen species regulated by LBH589 in K562 tumor cells. AEE788 selectively inhibits VEGF-induced angiogenesis without affecting bFGF-induced angiogenesis and significantly lowers the expression levels of pEGFR and pVEGFR in HT29 cecal cancer, without altering the expression of EGF, VEGF, EGFR, or VEGFR. When used in combination with CPT-11, it considerably inhibits lymphoma metastasis and suppresses the growth of Daoy, DaoyPt, and DaoyHER2 transplanted tumors by 51%, 45%, and 72%, respectively.
• Cell Research:
  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. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

c-Fms, cFms, c-Abl, BcrAbl, Apoptosis, AEE 788, AEE788, AEE-788, Inhibitor, HER2/ErbB2, HER1, Epidermal growth factor receptor, EGFR, ErbB-1, FLT1, NVP-AEE 788, NVP-AEE788, NVP-AEE-788, inhibit

Compound Identifiers

PubChem CID

10297043