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Stattic

现货
Catalog No.
A2224
STAT3抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
25mg
¥ 800.00
现货
100mg
¥ 2,000.00
现货

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Background

Stattic is a small molecule inhibitor of STAT3 with IC50 values of 2.562 ± 0.409 μM, 3.481 ± 0.953 μM, 2.282 ± 0.423 μM and 2.648 ± 0.542 μM, respectively, in UM-SCC-17B, OSC-19, Cal33 and UM-SCC-22B cell lines [1].

Stattic is reported to selectively inhibit dimerization, activation and nuclear translocation of STAT3. It can also induce the apoptosis of STAT3-dependent breast cancer cell lines [2].

The inhibition of STAT3 by Stattic results in decreased STAT3-mediated HIF-1 expression and subsequent radiosensitization of HNSCC cells. Inhibiting the STAT3 signaling pathway may represent an effective strategy in the treatment of HNSCC. The evidence of Stattic activity in vivo has also been found. Stattic pre-treatment sensitizes orthotopic xenograft HNSCC tumors to radiation, wich results in significantly reduced tumor growth, although this effect was not as dramatic as anticipated by the in vitro studies [1].

References:
[1] Makoto Adachi, Caixia Cui, Cristina T. Dodge, Mihir K. Bhayani, Stephen Y. Lai. Targeting STAT3 inhibits growth and enhances radiosensitivity in head and neck squamous cell carcinoma. Oral Oncology. 2012 July(48):1220-1226.

[2] Jochen Schust, Bianca Sperl, Angela Hollis, Thomas U. Mayer, and Thorsten Berg. Stattic: A Small-Molecule Inhibitor of STAT3 Activation and Dimerization. Chemistry & Biology. 2006(13):1235-1242.

文献引用

1. Linnan Yang, Jing Sun, et al. "Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment." Advanced Science. 16 February 2019.
2. Lee YC, Wang LJ, et al. "ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells." Cancer Lett. 2018 Jun 15;432:191-204. PMID:29913235
3. Kim W, Khan SK, et al. "Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis." J Clin Invest. 2017 Jan 3;127(1):137-152. PMID:27869648
4. Furtek SL, Matheson CJ, et al. "Evaluation of quantitative assays for the identification of direct signal transducer and activator of transcription 3 (STAT3) inhibitors." Oncotarget. 2016 Nov 22;7(47):77998-78008. PMID:27793003
5. Syn Kok Yeo, Jian Wen, Song Chen1, and Jun-Lin Guan, "Autophagy differentially regulates distinct breast cancer stem-like cells in murine models via EGFR/Stat3 and Tgfß/Smad signaling." Published OnlineFirst April 13, 2016.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt211.19
Cas No.19983-44-9
FormulaC8H5NO4S
Solubility≥10.6mg/mL in DMSO
Chemical Name6-nitro-1-benzothiophene 1,1-dioxide
SDFDownload SDF
Canonical SMILESC1=CC(=CC2=C1C=CS2(=O)=O)[N+](=O)[O-]
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

高通量筛选和荧光偏振检测

在约30°C下进行筛选。进行实验化合物与STAT1、STAT5和Lck SH2结构域结合的类似实验,从而验证筛选的特异性。在所有荧光偏振检测中,各缓冲液组分的终浓度分为10 mM HEPES(pH 7.5),1 mM EDTA,0.1% Nonidet P-40,50 mM NaCl和10% DMSO。二硫苏糖醇在抑制活性方面发挥着重要作用。多肽序列分别为:STAT3,5-羧基荧光素-GY(PO3H2)LPQTV-NH2;STAT1,5-羧基荧光素-GY(PO3H2)DKPHVL;STAT5,5-羧基荧光素-GY(PO3H2)LVLDKW和Lck,5-羧基荧光素-GY(PO3H2)EEIP。在30°C下进行特异性分析,使用150 nM蛋白(STAT1,STAT3和STAT5)。在37°C下进行特异性分析,使用370 nM蛋白(STAT3)或100 nM蛋白(Lck)。将蛋白与实验化合物加入Eppendorf管中,将其置于指定温度环境中孵育60分钟,然后加入相应的5-羧基荧光素标记多肽(终浓度为10 nM)。混合物至少平衡30分钟,然后于室温下测量。使用20×原液和DMSO将实验化合物稀释到指定浓度。使用SigmaPlot绘制结合曲线和抑制曲线。在独立实验中,所有竞争曲线都需要重复3次。

细胞实验 [2]:

细胞系

头颈部鳞状细胞癌(HNSCC)细胞系UM-SCC-17B、OSC-19、Cal33和UM-SCC-22B

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

0 ~ 100 M;24小时

实验结果

Stattic显著抑制STAT3的活化与表达,导致细胞存活与增殖减少以及放射敏感性增加。Stattic治疗也下调STAT3介导的HIF-1表达。

动物实验 [2]:

动物模型

UM-SCC-17B细胞异种移植小鼠模型

给药剂量

50 mg/kg;口服;每星期5次,持续4星期

实验结果

在鼠原位异种移植物中,口服给予Stattic有效抑制HNSCC肿瘤生长。肿瘤裂解物分析结果表明,STAT3磷酸化减少。

其他注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Jochen Schust, Bianca Sperl, Angela Hollis, Thomas U. Mayer, and Thorsten Berg. Stattic: A Small-Molecule Inhibitor of STAT3 Activation and Dimerization. Chemistry & Biology. 2006(13):1235-1242.

[2]. Makoto Adachi, Caixia Cui, Cristina T. Dodge, Mihir K. Bhayani, Stephen Y. Lai. Targeting STAT3 inhibits growth and enhances radiosensitivity in head and neck squamous cell carcinoma. Oral Oncology. 2012 July(48):1220-1226.

生物活性

描述 Stattic是STAT3的小分子抑制剂,在UM-SCC-17B、OSC-19、Cal33和UM-SCC-22B细胞系中的IC50值分别为2.562±0.409 μM、3.481±0.953 μM、2.282±0.423 μM和2.648±0.542 μM。
靶点 STAT3 STAT3 STAT3 STAT3    
IC50 2.562 ± 0.409 μM (UM-SCC-17B cell line) 3.481 ± 0.953 μM (OSC-19 cell line) 2.282 ± 0.423 μM (Cal33 cell line) 2.648 ± 0.542 μM (UM-SCC-22B cell line)    

质量控制

化学结构

Stattic

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