产品号 #72672_C
WNT通路抑制剂；抑制TNKS1和TNKS2
总览
XAV939是一种高效的针对tankyrase（TNKS） 1和2的小分子抑制剂（IC50分别= 11和4 nM）（Huang et al.）。通过抑制TNKS活性，XAV939提高了 axin-GSK3β复合物的蛋白水平，并促进SW480细胞中β-连环素（β-catenin）的降解（Huang et al.），从而抑制了WNT通路的下游作用。
分化
·诱导小鼠胚胎干细胞的中胚层祖细胞的心肌分化（Wang等）。
·与SMAD抑制剂LDN193189和SB431542一起使用，可促进人多能干细胞前脑分化（Maroof et al.）。
癌症研究
·抑制APC缺失、β-连环素依赖的DLD-1结直肠癌细胞的克隆形成（Huang et al.）。
细胞类型
癌细胞及细胞系，心肌细胞，PSC衍生，神经细胞，PSC衍生，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
研究领域
癌症，神经科学，干细胞生物学
CAS 编号
284028-89-3
化学式
C₁₄H₁₁F₃N₂OS
纯度
≥98%
通路
WNT
靶点
TNKS
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (4)
Publications (7)
Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells. Cell stem cell 2013 MAY
Abstract
Human pluripotent stem cells are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations: projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism, and epilepsy. Here, we demonstrate the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes, and migratory behaviors. Further differentiation in a murine cortical environment yields parvalbumin- and somatostatin-expressing neurons that exhibit synaptic inputs and electrophysiological properties of cortical interneurons. Our study defines the signals sufficient for modeling human ventral forebrain development in vitro and lays the foundation for studying cortical interneuron involvement in human disease pathology.
Cardiac induction of embryonic stem cells by a small molecule inhibitor of Wnt/β-catenin signaling. ACS chemical biology 2011 MAR
Abstract
In vitro differentiation of embryonic stem cells is tightly regulated by the same key signaling pathways that control pattern formation during embryogenesis. Small molecules that selectively target these developmental pathways, including Wnt, and BMP signaling may be valuable for directing differentiation of pluripotent stem cells toward many desired tissue types, but to date only few such compounds have been shown to promote cardiac differentiation. Here, we show that XAV939, a recently discovered small molecule inhibitor of Wnt/β-catenin signaling, can robustly induce cardiomyogenesis in mouse ES cells. Our results suggest that a timely administration of XAV939 immediately following the formation of mesoderm progenitor cells promotes cardiomyogenic development at the expense of other mesoderm derived lineages, including the endothelial, smooth muscle, and hematopoietic lineages. Given the critical role that Wnt/β-catenin signaling plays in many aspects of embryogenesis and tissue regeneration, XAV939 is a valuable chemical probe to dissect in vitro differentiation of stem cells and to explore their regenerative potential in a variety of contexts.
Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 2009 OCT
Abstract
The stability of the Wnt pathway transcription factor beta-catenin is tightly regulated by the multi-subunit destruction complex. Deregulated Wnt pathway activity has been implicated in many cancers, making this pathway an attractive target for anticancer therapies. However, the development of targeted Wnt pathway inhibitors has been hampered by the limited number of pathway components that are amenable to small molecule inhibition. Here, we used a chemical genetic screen to identify a small molecule, XAV939, which selectively inhibits beta-catenin-mediated transcription. XAV939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. Thus, our study provides new mechanistic insights into the regulation of axin protein homeostasis and presents new avenues for targeted Wnt pathway therapies.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 284028-89-3 |
| Chemical Formula | C₁₄H₁₁F₃N₂OS |
| Purity | ≥ 98% |
| Target | TNKS |
| Pathway | WNT |
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
