SU11274-PKI-SU11274-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESU11274Cat. No.: HY-12014CAS No.: 658084-23-2Synonyms: PKI-SU11274分式: CHClNOS分量: 568.09作靶點: c-Met/HGFR; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解

2、性數據體外實驗 DMSO : 100 mg/mL (176.03 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.40 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 SU11274種選擇性的 Met 抑制劑，IC50 值為 10 nM，對 PGDFR，EGFR 或 Tie2 沒有抑制作。IC50 & Target IC50: 10 nM (Met) 1體外研究 SU11274

3、 exhibits greater than 50-fold selectivity for Met versus Flk and more than 500 times selectivityversus other tyrosine kinases such as FGFR-1, c-src, PDGFbR, and EGFR. SU11274 inhibits thephosphorylation of key regulators of the PI3K pathway, including AKT, FKHR, or GSK3. SU11274 treatmentinhibits t

4、he growth of TPR-MET-transformed BaF3 cells in a dose-dependent manner with IC50 of 3 M inthe absence of interleukin 3, without growth inhibition of BaF3 cells transformed by other oncogenic tyrosinekinases, including BCR-ABL, TEL-JAK2, TEL-ABL, and TEL-PDGFR. In addition to cell growth, SU11274trea

5、tment significantly inhibits the migration of BaF3. TPR-MET cells by 44.8% and 80% at 1 M and 5 M,respectively. SU11274 inhibits HGF-dependent phosphorylation of Met as well as HGF-dependent cellproliferation and motility with an IC50 of 1-1.5 M. In H69 and H345 cells which have functional Met recep

6、tor,SU11274 inhibits the HGF-induced cell growth with IC50 of 3.4 M and 6.5 M, respectively. SU11274induces G1 cell cycle arrest with cells in G1 phase increased from 42.4% to 70.6% at 5 M, and inducescaspase-dependent apoptosis by 24% at 1 M 2. SU11274 inhibits cell viability in c-Met-expressing no

7、n-small cell lung cancer (NSCLC) cells with IC50 values of 0.8-4.4 M, and abrogates hepatocyte growthfactor-induced phosphorylation of c-Met and its downstream signaling 3.PROTOCOLKinase Assay 1 A chimeric protein is constructed containing the cytoplasmic domain of human c-Met fused to Glutathione S

8、-transferase (GST) and expressed in SF9 cells. The c-Met kinase GST-fusion protein is used for an ELISA-based Met biochemical assay using the random copolymer poly(Glu:Tyr) (4:1) immobilized on microtiterplates as a substrate. IC50 value is determined with various concentrations of SU11274 in a buff

9、er containing5 M ATP and 10 mM MnCl2, 50 mM HEPES (pH 7.5), 25 mM NaCl, 0.01% BSA, and 0.1 mM Naorthovanadate. The kinase reaction is performed for 5 minutes at room temperature. The extent of substratephosphorylation is measured using horseradish peroxidase-conjugated anti-pTyr antibodies.MCE has n

10、ot independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Cells are exposed to various concentrations of SU11274 in the presence or absence of HGF for 24, 48, and72 hours. The number of viable cells is determined using the MTT assay or trypan blue exclusion.

11、Cell Cycleand apoptosis are measured by fluorescence-activated cell sorter analysis via propidium iodide staining andAnnexin V-positive staining, respectively.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發(fā)表的科研獻 Cancer Cell Int. 2019 Jul. Harvard

12、 Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Wang X, et al. Potent and selective inhibitors of the Met hepatocyte growth factor/scatter factor (HGF/SF) receptor tyrosine kinaseblock HGF/SF-induced

13、tumor cell growth and invasion. Mol Cancer Ther, 2003, 2(11):1085-1092.2. Sattler M, et al. A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase.Cancer Res, 2003, 63(17), 5462-5469.3. Ma PC, et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA innon-small cell lung cancer. Cancer Res, 2005, 65(4), 1479-1488.