EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73512_C
WNT通路激活剂；抑制GSK3β
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总览
TWS119是一种强效的二取代吡咯嘧啶类糖原合酶激酶3β（GSK3β）抑制剂，IC₅₀值为30 nM，Kd为126 nM（Ding et al.）。GSK3是一种丝氨酸/苏氨酸激酶，是WNT通路的关键抑制剂；因此，TWS119可作为WNT通路的激活剂。
维持培养
·维持Wistar大鼠肝星状细胞的双效静息状态（Kordes et al.）。
分化
·诱导小鼠胚胎癌和胚胎干细胞向神经元分化（Ding et al.）。
·诱导小鼠或人CD8+ T细胞产生T记忆干细胞样（T-SCM）细胞，并有证据表明，在小鼠来源的T-SCM过继转移后，T-SCM的持久性、增殖和抗肿瘤活性均有所增强（Forget et al.; Gattinoni et al.）。
癌症研究
·抑制人肺泡横纹肌肉瘤细胞增殖并诱导其凋亡（Zeng et al.）。
细胞类型
癌细胞及细胞系，多能干细胞，T 细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
应用
分化，培养
研究领域
癌症，免疫，干细胞生物学
CAS 编号
601514-19-6
化学式
C₁₈H₁₄N₄O₂
纯度
≥ 90%
通路
WNT
靶点
GSK3β
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
应用领域
本产品专为以下研究领域设计，适用于工作流程中的高亮阶段。探索这些工作流程，了解更多我们为各研究领域提供的其他配套产品。
相关材料与文献
技术资料 (3)
文献 (5)
Synthetic small molecules that control stem cell fate.
Proceedings of the National Academy of Sciences of the United States of America 2003
Abstract
In an attempt to better understand and control the processes that regulate stem cell fate,we have set out to identify small molecules that induce neuronal differentiation in embryonic stem cells (ESCs). A high-throughput phenotypic cell-based screen of kinase-directed combinatorial libraries led to the discovery of TWS119,a 4,6-disubstituted pyrrolopyrimidine that can induce neurogenesis in murine ESCs. The target of TWS119 was shown to be glycogen synthase kinase-3beta (GSK-3beta) by both affinity-based and biochemical methods. This study provides evidence that GSK-3beta is involved in the induction of mammalian neurogenesis in ESCs. This and such other molecules are likely to provide insights into the molecular mechanisms that control stem cell fate,and may ultimately be useful to in vivo stem cell biology and therapy.
Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells.
Biochemical and biophysical research communications 2008
Abstract
It is well known that hepatic stellate cells (HSC) develop into cells,which are thought to contribute to liver fibrogenesis. Recent data suggest that HSC are progenitor cells with the capacity to differentiate into cells of endothelial and hepatocyte lineages. The present study shows that beta-catenin-dependent canonical Wnt signaling is active in freshly isolated HSC of rats. Mimicking of the canonical Wnt pathway in cultured HSC by TWS119,an inhibitor of the glycogen synthase kinase 3beta,led to reduced beta-catenin phosphorylation,induced nuclear translocation of beta-catenin,elevated glutamine synthetase production,impeded synthesis of alpha-smooth muscle actin and Wnt5a,but promoted the expression of glial fibrillary acidic protein,Wnt10b,and paired-like homeodomain transcription factor 2c. In addition,canonical Wnt signaling lowered DNA synthesis and hindered HSC from entering the cell cycle. The findings demonstrate that beta-catenin-dependent Wnt signaling maintains the quiescent state of HSC and,similar to stem and progenitor cells,influences their developmental fate.
Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells.
Nature medicine 2009
Abstract
Self-renewing cell populations such as hematopoietic stem cells and memory B and T lymphocytes might be regulated by shared signaling pathways. The Wnt-beta-catenin pathway is an evolutionarily conserved pathway that promotes hematopoietic stem cell self-renewal and multipotency by limiting stem cell proliferation and differentiation,but its role in the generation and maintenance of memory T cells is unknown. We found that induction of Wnt-beta-catenin signaling by inhibitors of glycogen sythase kinase-3beta or the Wnt protein family member Wnt3a arrested CD8(+) T cell development into effector cells. By blocking T cell differentiation,Wnt signaling promoted the generation of CD44(low)CD62L(high)Sca-1(high)CD122(high)Bcl-2(high) self-renewing multipotent CD8(+) memory stem cells with proliferative and antitumor capacities exceeding those of central and effector memory T cell subsets. These findings reveal a key role for Wnt signaling in the maintenance of 'stemness' in mature memory CD8(+) T cells and have major implications for the design of new vaccination strategies and adoptive immunotherapies.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 601514-19-6 |
| Chemical Formula | C₁₈H₁₄N₄O₂ |
| 纯度 | ≥ 90% |
| Target | GSK3β |
| Pathway | WNT |
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