SNS-314 Mesylate
(Synonyms: N-(3-氯苯基)-N'-[5-[2-(噻吩并3,2-D]嘧啶-4-基氨基)乙基]-2-噻唑基]脲甲磺酸盐(1:1)) 目录号 : GC13837
A pan-Aurora kinase inhibitor
Cas No.:1146618-41-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | A homogeneous time-resolved fluorescence (HTRF)-based biochemical IC50 assay is used to test for the kinase activity of the three isoforms of Aurora (A, B, and C) in the presence of SNS-314. A biotin-conjugated histone H3 peptide is used as substrate. Aurora-A kinase (7.5 nM) is assayed in 10 mM Tris–HCl pH 7.2, 10 mM MgCl2, 0.1% BSA, 0.05% Tween 20, 1 mM DTT, 120 nM biotinylated peptide ARTKQTARKSTGGKAPRKQLA-GGK-biotin, 6 μM ATP (2×the Km for the enzyme) for 1 h at 25°C. The reaction is stopped with 200 mM EDTA. Aurora-B and Aurora-C are assayed at 5 nM enzyme concentration, 120 nM biotinylated peptide, and 300 lM ATP (29 the Km for the enzymes) for 1 h at 25°C[2]. |
Cell experiment: | HCT116 cells are treated with various concentrations of SNS-314 for 96 hours. cells are incubated with BrdU for 2 h at 37°C. Cell proliferation activity is evaluated by chemiluminescence detection of BrdU incorporated in DNA[2]. |
Animal experiment: | Mice: Tumor mice are treated with vehicle or SNS-314. Animals are weighed, monitored for signs or symptoms of toxic effects, and measured for tumor volumes twice weekly until an end point is met[2]. |
References: [1]. Oslob JD, et al. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4. | |
SNS-314 is an ATP-competitive and selective inhibitor of aurora kinases with IC50 values of 9 nM, 31 nM and 3 nM against Aurora A, Aurora B and Aurora C, respectively [1 and 2].
Aurora kinases are serine/threonine kinases that regulate mitosis of cells. They are found to be associated with the onset and propagation of cancer and over-expressed in various tumor cell lines such as melanoma, ovarian, colon, pancreatic and breast tumors. Therefore, aurora kinases are being evaluated as potential targets in cancer therapy .As a potent inhibitor of aurora kinase, SNS-314inhibited proliferation in a broad panel of tumor cell lines and showed potent anti-tumor activity in mice bearing HCT116 xenografts. Besides that, a mechanism of its action was found to be inhibiting the phosphorylation of histoneH3 at Ser10 [1 and 2].
In the FRET-based biochemical assay, SNS-314inhibited Aurora A, B and C with IC50 values of 9, 31 and 3 nM, respectively. When tested against a panel of 219 kinases, SNS-314 only inhibited 24 kinases of them by 65% or above. It suggested that SNS-314 was a selective inhibitor of aurora kinase. In cell-based assays, SNS-314 blocked the proliferation of cancer cells with IC50 value in the range from 1.8 nM (A2780) to 24 nM (HT29). In HCT-116 cells, SNS-314 treatment for 16 hours resulted in distinct cell-cycle defects [2].
In human tumor xenograft mouse models, administration of SNS-314 exerted significant anti-tumor activities against xenografts of PC-3, H1299, A2780, MDA-MB-231 and A375 cells. The TGI value achieved between 54% and 91% when the dose was 170 mg/kg. The administration also caused a profound and sustained inhibition of pHH3 which was a substrate of Aurora B [2].
References:
[1] Oslob J D, Romanowski M J, Allen D A, et al. Discovery of a potent and selective aurora kinase inhibitor. Bioorganic & medicinal chemistry letters, 2008, 18(17): 4880-4884.
[2] Arbitrario J P, Belmont B J, Evanchik M J, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer chemotherapy and pharmacology, 2010, 65(4): 707-717.
| Cas No. | 1146618-41-8 | SDF | |
| 别名 | N-(3-氯苯基)-N'-[5-[2-(噻吩并3,2-D]嘧啶-4-基氨基)乙基]-2-噻唑基]脲甲磺酸盐(1:1) | ||
| 化学名 | 1-(3-chlorophenyl)-3-[5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-1,3-thiazol-2-yl]urea;methanesulfonic acid | ||
| Canonical SMILES | CS(=O)(=O)O.C1=CC(=CC(=C1)Cl)NC(=O)NC2=NC=C(S2)CCNC3=NC=NC4=C3SC=C4 | ||
| 分子式 | C18H15ClN6OS2.CH4O3S | 分子量 | 527.04 |
| 溶解度 | ≥ 26.35 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8974 mL | 9.4869 mL | 18.9739 mL |
| 5 mM | 0.3795 mL | 1.8974 mL | 3.7948 mL |
| 10 mM | 0.1897 mL | 0.9487 mL | 1.8974 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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