| 名稱 | SNS-314 Mesylate |
| 描述 | SNS-314 Mesylate (SNS-314) is an effective and specific Aurora A/B/C inhibitor (IC50: 9/31/3 nM). It is less inhibition of Trk A/B, Fms, Flt4, c-Raf, Axl, and DDR2. |
| 細胞實驗 | Viability is measured using the CellTiter-Blue cell viability assay. Cells are treated as described above, although with a 5-day incubation period. Cytotoxicity is determined by measuring intracellular ATP using the CellTiter-Glo Luminescence Cell Viability Assay. Cells are seeded in white 96-well tissue culture plates at a density of 1.5-2 × 103 cells/well, and a serial dilution of SNS-314 is dosed in combination with fixed concentrations of either docetaxel or vincristine for a total of 72 hours. Viability is determined as the ratio between the ATP in treated cells versus control cells. Apoptosis is measured using the caspase-Glo 3/7 system. Cells are plated in white 96-well plates as described above and treated first with SNS-314 for 24 hours, washed with 200 μL of 1× PBS, and fresh medium is added with the second agent for 24 hours.(Only for Reference) |
| 激酶實驗 | Aurora-A Kinase Assay: Humanized mouse Aurora A (amino acids 107-403) is expressed in E. coli as described previously. For IC50 assays, compounds are titrated three-fold in DMSO and diluted 12.5-fold into assay buffer (10 mM Tris HCl pH 7.2, 10 mM MgCl2, 0.05% NaN3, 0.01% Tween-20, and 0.1% BSA). Compounds are then diluted 4-fold into assay buffer containing Aurora A and FAM-PKAtide at final concentrations of 2 nM and 50 nM, respectively. The kinase reaction is initiated by adding ATP in assay buffer at a final concentration of 10 mM and incubated at 21 °C for 25 minutes. As a positive control, DMSO is added instead of compound and as a negative control assay buffer is added instead of Aurora A. Both control reactions are conducted in triplicate. To detect phosphorylated PKAtide, the kinase reaction is combined with Progressive Binding Solution (1:400 Progressive Binding Reagent, 1 × Buffer A, Molecular Devices) in a 1:3 ratio. The mixture is incubated for 30 minutes at 21 °C and the plate is scanned on an Analyst AD with excitation at 485 nm and emission at 530 nm. The percent relative enzymatic activity is calculated by normalizing the mP value for each well to the average positive control. Relative enzymatic activity values are plotted as a function of the logarithm of compound concentration and IC50 values are generated in GraphPad Prism software using a sigmoidal dose-response curve-fit. IC50's are calculated as the concentration of compound at which enzymatic activity i |
| 體外活性 | 在HCT116 結(jié)腸移植瘤中,SNS-314的抗癌效果明顯和持久.在人類乳腺癌,前列腺癌,肺癌(H1299和Calu-6),卵巢癌及惡性黑色素瘤的鼠移植瘤中,SNS-314（170 mg/kg）對腫瘤生長抑制率為54-91%. |
| 體內(nèi)活性 | 用SNS-314和吉西他濱、卡鉑、道諾霉素、氟尿嘧啶和SN-38連續(xù)處理使抗增殖效果加強,SNS-314和吉西他濱,多西他賽,或長春新堿聯(lián)用有協(xié)同效果。SNS-314對腫瘤細胞系具有明顯抑制作用（IC50：1.8-24 nM）, 且不依賴于Aurora-A或Aurora-B的相對蛋白水平。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 52.7 mg/mL (100 mM)
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| 關(guān)鍵字 | HeLa | SNS314 Mesylate | H-1299 | SNS 314 Mesylate | PC-3 | ovarian cancer cell | A2780 | SNS-314 Mesylate | Aurora Kinase | Inhibitor | SNS 314 | inhibit | HT29 | SNS314 | HCT116 |
| 相關(guān)產(chǎn)品 | TCS7010 | Palmatine | MBM-55S | KW-2449 | Alisertib | MK-8745 | TAK-901 | SC-514 | Barasertib-HQPA | CCT129202 | Palmatine chloride | SP600125 |
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