Stattic
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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[1]。
据报道,stattic选择性抑制STAT3的二聚化、激活和核易位。Stattic也诱导STAT3依赖性乳腺癌细胞系的细胞凋亡[2]。
Stattic对STAT3的抑制导致STAT3介导的HIF-1表达的减少,及随后头颈部鳞状细胞癌(HNSCC)细胞的放射增敏作用。抑制STAT3信号通路可能代表了一种有效的用于治疗HNSCC的策略。Stattic在体内的活性也被发现。Stattic预处理可增加原位异种移植HNSCC肿瘤的放射增敏作用,显著减少肿瘤生长,尽管该效果不如体外研究预期的那么显著[1]。
参考文献:
[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.
- 1. Weibo Zhong, Kaihui Wu, et al. "Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis." Microbiome. 2022 Jun 16;10(1):94. PMID: 35710492
- 2. Ying Zhang, Cong Liu, et al. "IL-22 promotes tumor growth of breast cancer cells in mice." Aging (Albany NY). 2020 Jul 15; 12(13): 13354–13364. PMID: 32649314
- 3. Li L, Shang L, et al. "Janus kinase inhibitor ruxolitinib blocks thymic regeneration after acute thymus injury." Biochem Pharmacol. 2019 Nov 11:113712. PMID: 31726048
- 4. Zhang Q, Liu RX, et al. "Exosomal transfer of p-STAT3 promotes acquired 5-FU resistance in colorectal cancer cells." J Exp Clin Cancer Res. 2019 Jul 19;38(1):320. PMID: 31324203
- 5. Linnan Yang, Jing Sun, et al. "Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment." Advanced Science. 16 February 2019.
- 6. 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
- 7. 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
- 8. 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
- 9. Syn Kok Yeo, Jian Wen, et al. "Autophagy differentially regulates distinct breast cancer stem-like cells in murine models via EGFR/Stat3 and Tgfß/Smad signaling." Published OnlineFirst April 13, 2016.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 211.19 |
Cas No. | 19983-44-9 |
Formula | C8H5NO4S |
Solubility | insoluble in H2O; insoluble in EtOH; ≥10.56 mg/mL in DMSO |
Chemical Name | 6-nitro-1-benzothiophene 1,1-dioxide |
SDF | Download SDF |
Canonical SMILES | C1=CC(=CC2=C1C=CS2(=O)=O)[N+](=O)[O-] |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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) |
质量控制和MSDS
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