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SB216763

WNT通路激活剂;抑制GSK3α和GSK3β

产品号 #(选择产品)

产品号 #72872_C

WNT通路激活剂;抑制GSK3α和GSK3β

总览

SB216763 是一种可透过细胞膜的 ATP 竞争性糖原合酶激酶 3α(GSK3α,IC₅₀ = 34 nM)及同工酶 GSK3β 的抑制剂(Coghlan et al.)。GSK3是一种丝氨酸/苏氨酸蛋白激酶,会被多种细胞外刺激的抑制,如胰岛素、生长因子、细胞命运决定因子和细胞粘附。

维持和自我更新
·在无白血病抑制因子(LIF)的情况下,将小鼠胚胎干细胞(ES)与小鼠胚胎成纤维细胞(MEFs)共培养,维持在未分化的多能状态长达两个月(Kirby et al.)。
·促进原代小鼠视网膜干细胞的增殖(Inoue et al.)。
·增加小鼠大脑中的神经祖细胞增殖(Mao et al.)。
·在成年小鼠的体内和体外模型中,促进神经干细胞(NSCs)的对称分裂(Piccin and Morshead)。
·抑制人间充质干细胞(MSCs)向脂肪细胞的分化(Shen et al.)。
·促进主动脉-性腺-中肾(AGM)外植体培养中造血干细胞(HSC)的生成(Ruiz-Herguido et al.)。

分化
·增强胰岛素诱导的小鼠肌母细胞静息储备细胞的分化(Rochat et al.)。
·刺激大鼠神经球的NSC的分化(Maurer et al.)。
·诱导人神经祖细胞(NPC)向神经元分化(Lange et al.)。
·促进小鼠造血祖细胞(HPCs)向树突状细胞分化(Zhou et al.)。

癌症研究
·诱导人胶质母细胞瘤细胞分化并减少癌症干细胞群(Korur et al.)。

细胞类型
癌细胞及细胞系,树突状细胞(DCs),造血干/祖细胞,间充质干/祖细胞,肌源干/祖细胞,神经干/祖细胞,多能干细胞
 
种属
人,小鼠,非人灵长类,其它细胞系,大鼠
 
应用
分化,扩增,培养
 
研究领域
癌症,神经科学,干细胞生物学
 
CAS 编号
280744-09-4
 
化学式
C₁₉H₁₂Cl₂N₂O₂
 
纯度
≥98%
 
通路
WNT
 
靶点
GSK
 

产品说明书及文档

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Document Type
Product Name
Catalog #
Lot #
Language
Product Name
SB216763
Catalog #
72872
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
SB216763
Catalog #
72872
Lot #
All
Language
English

相关材料与文献

技术资料 (3)

文献 (12)

Hematopoietic stem cell development requires transient Wnt/β-catenin activity. Ruiz-Herguido C et al. The Journal of experimental medicine 2012 JUL

Abstract

Understanding how hematopoietic stem cells (HSCs) are generated and the signals that control this process is a crucial issue for regenerative medicine applications that require in vitro production of HSC. HSCs emerge during embryonic life from an endothelial-like cell population that resides in the aorta-gonad-mesonephros (AGM) region. We show here that β-catenin is nuclear and active in few endothelial nonhematopoietic cells closely associated with the emerging hematopoietic clusters of the embryonic aorta during mouse development. Importantly, Wnt/β-catenin activity is transiently required in the AGM to generate long-term HSCs and to produce hematopoietic cells in vitro from AGM endothelial precursors. Genetic deletion of β-catenin from the embryonic endothelium stage (using VE-cadherin-Cre recombinase), but not from embryonic hematopoietic cells (using Vav1-Cre), precludes progression of mutant cells toward the hematopoietic lineage; however, these mutant cells still contribute to the adult endothelium. Together, those findings indicate that Wnt/β-catenin activity is needed for the emergence but not the maintenance of HSCs in mouse embryos.
Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells. Kirby LA et al. PloS one 2012 JAN

Abstract

Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months.
Wnt signaling regulates symmetry of division of neural stem cells in the adult brain and in response to injury. Piccin D and Morshead CM Stem cells (Dayton, Ohio) 2011 MAR

Abstract

Neural stem cells comprise a small population of subependymal cells in the adult brain that divide asymmetrically under baseline conditions to maintain the stem cell pool and divide symmetrically in response to injury to increase their numbers. Using in vivo and in vitro models, we demonstrate that Wnt signaling plays a role in regulating the symmetric divisions of adult neural stem cells with no change in the proliferation kinetics of the progenitor population. Using BAT-gal transgenic reporter mice to identify cells with active Wnt signaling, we demonstrate that Wnt signaling is absent in stem cells in conditions where they are dividing asymmetrically and that it is upregulated when stem cells are dividing symmetrically, such as (a) during subependymal regeneration in vivo, (b) in response to stroke, and (c) during colony formation in vitro. Moreover, we demonstrate that blocking Wnt signaling in conditions where neural stem cells are dividing symmetrically inhibits neural stem cell expansion both in vivo and in vitro. Together, these findings reveal that the mechanism by which Wnt signaling modulates the size of the stem cell pool is by regulating the symmetry of stem cell division.

更多信息

更多信息
种属 Human, Mouse, Non-Human Primate, Other, Rat
Cas Number 280744-09-4
Chemical Formula C₁₉H₁₂Cl₂N₂O₂
纯度 ≥ 98%
Target GSK
Pathway WNT
质量保证:

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