1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAEE788Cat. No.: HY-10045CAS No.: 497839-62-0Synonyms: NVP-AEE 788分式: CHN分量: 440.58作靶點: EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO

2、: 50 mg/mL (113.49 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.67 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.67 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每

3、種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.67 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 AEE788是EGFR和ErbB2的抑制劑，IC50值分別為2和6 nM。IC50 & Target EGFR ErbB22 nM (IC50) 6 nM (IC50)體外研究 AEE788 inhibits EGFR and VEGF receptor tyrosine kinases in the nM range (IC50:EGFR 2 nm, ErbB2 6 nm,KDR 77 nm, and

4、Flt-1 59 nm). In cells, growth factor-induced EGFR and ErbB2 phosphorylation is alsoefficiently inhibited (IC50:11 and 220 nm, respectively). AEE788 demonstrates antiproliferative activityagainst a range of EGFR and ErbB2-overexpressing cell lines (including EGFRvIII-dependent lines) andinhibits the

5、 proliferation of epidermal growth factor- and VEGF-stimulated human umbilical vein endothelialcells 1. Treatment of cutaneous SCC cells with AEE788 leads to dose-dependent inhibition of EGFR andVEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis 2.體內(nèi)研究 AEE788 efficiently inhibits

6、 growth factor-induced EGFR and ErbB2 phosphorylation in tumors for 72 h.AEE788 also inhibits VEGF-induced angiogenesis in a murine implant model 1. In mice treated withAEE788, tumor growth is inhibited by 54% at 21 days after the start of treatment compared with control mice2.PROTOCOLKinase Assay 1

7、 The invitro kinase assays are performed in 96-well plates (30 L) at ambient temperature for 1545 minusing the recombinant glutathione S-transferase-fused kinase domains (4100 ng, depending on specificactivity). 33PATP is used as phosphate donor and polyGluTyr-(4:1) peptide as acceptor. Assays areop

8、timized for each kinase using the following ATP concentrations: 1.0 M (c-Kit, c-Met, c-Fms, c-Raf-1, andRET), 2.0 M (EGFR, ErbB2, ErbB3, and ErbB4), 5.0 M (c-Abl), 8.0 M (Flt-1, Flt-3, Flt-4, Flk, KDR, FGFR-1, and Tek), 10.0 M (PDGF receptor-, protein kinase C-, and cyclin-dependent kinase 1), and 2

9、0.0 M (c-Src and protein kinase A). The reaction is terminated by the addition of 20 L 125 mM EDTA. Thirty L (c-Abl, c-Src, insulin-like growth factor-1R, RET-Men2A, and RET-Men2B) or 40 L (all other kinases) of thereaction mixture is transferred onto Immobilon-polyvinylidene difluoride membrane, pr

10、esoaked with 0.5%H3PO4 and mounted on a vacuum manifold. Vacuum is then applied and each well rinsed with 200 L 0.5%H3PO4. Membranes are removed and washed four times. Dried membranes are counted. IC50 arecalculated by linear regression analysis of the percentage inhibition and are averages of at le

11、ast threedeterminations 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 AEE788 is dissolved in 90% polyethylene glycol 300 plus 10% 1-methyl-2-pyrrolidinone to a concentration of6.25 mg/mL. Tumor cells are seeded into 96-well plates in co

12、mplete medium and allowed to attach for 242/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEhours. The cultures are re-fed with medium with 2% serum. After 24 hours, cells are treated with differentconcentrations (0-2 M) of AEE788 (negative control with DMSO alone) for 72 hours. After a 2-hourincubat

13、ion in medium containing 0.42 mg/mL MTT, the cells are lysed in 100 L DMSO. The conversion ofMTT to formazan is measured at an absorbance of 570 nm 2MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: AEE788 is diluted in DMSO and diluted in th

14、e optimal medium. BALB/c mice bearing s.c. A-431Administration 1 squamous tumors (3 animals/group) or HC11-NeuT-driven breast tumors (2 animals/group) are dosed orallywith 30 mg/kg of AEE788 or vehicle once daily for 5 days. At different time points after the end of compoundtreatment and before sacr

15、ificing the animals the mice are given i.v. 500 g EGF/kg body weight or 0.2 ml0.9% w/v NaCl as vehicle control. Five min after EGF administration, the mice are sacrificed, tumors areremoved 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 S

16、ci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Oncol Rep. 2018 Nov;40(5):2944-2954. Int J Clin Exp Med. 2016;9(8):15892-15899.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Traxler P, et al. AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosinekinase 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 cellcarcinoma xenografts in