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  • SNS-314 Mesylate
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SNS-314 Mesylate

A pan-Aurora kinase inhibitor

原价
¥712-9850
价格
570-7880
SNS-314 Mesylate的二维码

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  • 货号: ajci11916
  • CAS: 1146618-41-8
  • 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)
  • 分子式: C18H15ClN6OS2.CH4O3S
  • 分子量: 527.04
  • 纯度: >98%
  • 溶解度: ≥ 26.35 mg/mL in DMSO
  • 储存: Store at -20°C
  • 库存: 现货

Background

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].
参考文献:
[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.

Protocol

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].

参考文献:

[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.
[2]. Arbitrario JP, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.

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