TWS119

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Chemical Structure| 601514-19-6 同义名 : -
CAS号 : 601514-19-6
货号 : A604058
分子式 : C18H14N4O2
纯度 : 99%
分子量 : 318.329
MDL号 : MFCD09037535
存储条件：

Pure form Keep in dark place,Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(157.07 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 2.4 mg/mL clear

PO 0.5% CMC-Na 32 mg/mL suspension

生物活性
靶点

  • GSK-3β

    GSK-3β, IC50:30 nM
描述 Glycogen synthase kinase 3β (GSK-3β), a component of the adenomatous polyposis coli/axin/GSK-3β complex, is involved in the ubiquitination and proteasomal degradation of β-catenin, which is the key molecule of the Wnt/β-catenin pathway [3]. Wnt/β-catenin pathway plays a critical role in carcinogenesis, embryonic development, i and insulin sensitivity[4]. TWS119 is a specific inhibitor of GSK-3β, its tight binding to GSK-3 was quantified by SPR and further demonstrated by its potent GSK-3 kinase inhibitory activity (IC50=30 nM) [5]. In vitro study revealed that treatment with TWS119 at dose 10 μM for 24 h of incubation not only significantly attenuated mRNA level of CD16 and increased the mRNA expression of CD206, but also reduced the percentage of CD16/32 positive cells and increased the percentage of CD206 positive cells in microglia cells stimulated by LPS plus IFN-γ, indicating a direct modulating effect of TWS119 on switch of microglial polarization from pro-inflammatory phenotype to antiinflammatory phenotype[6]. Another in vitro finding showed that TWS119 at dose of 7μM enhanced IL-2 production in Tcm cells from TILs, increased IL-2-secreting CD4+ Tem cells in TILs, and promoted the proliferation of CD8+ Teff cells in TILs from human lung cancer[7]. Furthermore, TWS119 had the ability to inhibit the activities of PC-3 cells and SW620 cells, suggesting its anticancer effect on prostate and colon cancer cells [8]. In an HCT116 xenograft tumor model, the tumor growth in BALB/c nude mice which received intratumoural injection with γδT cells pretreated with 2.0 μM of TWS119 was slower than the other groups, indicating its potent antitumor efficacy in vivo[9]. TWS119 ameliorated microglia-mediated neuroinflammatory status following ischemic stroke and promoted angiogenesis by modulating microglia to anti-inflammatory phenotype[6].
作用机制 TWS119 binds to GSK-3β then activates the canonical Wnt-β catenin signaling pathway to result in β catenin accumulation, which leads to the expression of genes downstream of canonical Wnt signaling[10].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
RAW 264.7 0-10000ng/ml Cytotoxicity Assay 24 h induces cell death in a dose dependent manner 24330853
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.14mL

0.63mL

0.31mL

15.71mL

3.14mL

1.57mL

31.41mL

6.28mL

3.14mL
参考文献

[1]Muralidharan S, Hanley PJ, et al. Activation of Wnt signaling arrests effector differentiation in human peripheral and cord blood-derived T lymphocytes. J Immunol. 2011 Nov 15;187(10):5221-32.

[2]Kordes C, Sawitza I, et al. Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells. Biochem Biophys Res Commun. 2008 Feb 29;367(1):116-23.

[3] Wang W. GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats. Mol Neurobiol. 2016 Dec;53(10):7028-7036. doi: 10.1007/s12035-015-9607-2. Epub 2015 Dec 15.

[4]Wnt signaling pathway

[5] Ding S. Synthetic small molecules that control stem cell fate. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7632-7. doi: 10.1073/pnas.0732087100. Epub 2003 Jun 6.

[6] Song D. Wnt canonical pathway activator TWS119 drives microglial anti-inflammatory activation and facilitates neurological recovery following experimental stroke. J Neuroinflammation. 2019 Dec 6;16(1):256. doi: 10.1186/s12974-019-1660-8.

[7] Tang YY. Effects of Glycogen Synthase Kinase-3β Inhibitor TWS119 on Proliferation and Cytokine Production of TILs From Human Lung Cancer. J Immunother. 2018 Sep;41(7):319-328. doi: 10.1097/CJI.0000000000000234.

[8] Sun A. GSK-3β controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells. Prostate. 2016 Feb;76(2):172-83. doi: 10.1002/pros.23106. Epub 2015 Oct 6.

[9] Chen YQ. Wnt pathway activator TWS119 enhances the proliferation and cytolytic activity of human γδT cells against colon cancer. Exp Cell Res. 2018 Jan 1;362(1):63-71. doi: 10.1016/j.yexcr.2017.11.003. Epub 2017 Nov 16.

[10] Muralidharan S, Hanley PJ. Activation of Wnt signaling arrests effector differentiation in human peripheral and cord blood-derived T lymphocytes. J Immunol. 2011 Nov 15;187(10):5221-32. doi: 10.4049/jimmunol.1101585. Epub 2011 Oct 19.