产品号 #72542_C
WNT 通路抑制剂；抑制豪猪蛋白 (Porcupine)
总览
WNT 生成抑制剂 3 (IWP-3) 通过抑制豪猪蛋白 (Porcupine) 来抑制 WNT 信号传导。豪猪蛋白是一种膜结合 O-酰基转移酶，负责对 WNT 蛋白进行棕榈酰化，而棕榈酰化对 WNT 信号传导能力和分泌至关重要（Chen et al.）。IWP-3 在体外可抑制 WNT 通路活性，IC50 值为 40 nM （Chen et al.）。
分化
·通过添加BMP4和激活素A，促进人胚胎干细胞向中胚层诱导的心肌细胞分化（Willems et al.）。
别名
Wnt 生成抑制剂-3
细胞类型
心肌细胞，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
干细胞生物学
CAS 编号
687561-60-0
化学式
C₂₂H₁₇FN₄O₂S₃
分子量
484.6 克/摩尔
纯度
≥98%
通路
WNT
靶点
Porcupine
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 (3)
Publications (5)
Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Circulation research 2011 AUG
Abstract
RATIONALE: Human embryonic stem cells can form cardiomyocytes when cultured under differentiation conditions. Although the initiating step of mesoderm formation is well characterized, the subsequent steps that promote for cardiac lineages are poorly understood and limit the yield of cardiomyocytes. OBJECTIVE: Our aim was to develop a human embryonic stem cell-based high-content screening assay to discover small molecules that drive cardiogenic differentiation after mesoderm is established to improve our understanding of the biology involved. Screening of libraries of small-molecule pathway modulators was predicted to provide insight into the cellular proteins and signaling pathways that control stem cell cardiogenesis. METHODS AND RESULTS: Approximately 550 known pathway modulators were screened in a high-content screening assay, with hits being called out by the appearance of a red fluorescent protein driven by the promoter of the cardiac-specific MYH6 gene. One potent small molecule was identified that inhibits transduction of the canonical Wnt response within the cell, which demonstrated that Wnt inhibition alone was sufficient to generate cardiomyocytes from human embryonic stem cell-derived mesoderm cells. Transcriptional profiling of inhibitor-treated compared with vehicle-treated samples further indicated that inhibition of Wnt does not induce other mesoderm lineages. Notably, several other Wnt inhibitors were very efficient in inducing cardiogenesis, including a molecule that prevents Wnts from being secreted by the cell, which confirmed that Wnt inhibition was the relevant biological activity. CONCLUSIONS: Pharmacological inhibition of Wnt signaling is sufficient to drive human mesoderm cells to form cardiomyocytes; this could yield novel tools for the benefit of pharmaceutical and clinical applications.
Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nature chemical biology 2009 FEB
Abstract
The pervasive influence of secreted Wnt signaling proteins in tissue homeostasis and tumorigenesis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. By screening a diverse synthetic chemical library, we have discovered two new classes of small molecules that disrupt Wnt pathway responses; whereas one class inhibits the activity of Porcupine, a membrane-bound acyltransferase that is essential to the production of Wnt proteins, the other abrogates destruction of Axin proteins, which are suppressors of Wnt/beta-catenin pathway activity. With these small molecules, we establish a chemical genetic approach for studying Wnt pathway responses and stem cell function in adult tissue. We achieve transient, reversible suppression of Wnt/beta-catenin pathway response in vivo, and we establish a mechanism-based approach to target cancerous cell growth. The signal transduction mechanisms shown here to be chemically tractable additionally contribute to Wnt-independent signal transduction pathways and thus could be broadly exploited for chemical genetics and therapeutic goals.
Wnt/beta-catenin signaling in development and disease. Cell 2006 NOV
Abstract
A remarkable interdisciplinary effort has unraveled the WNT (Wingless and INT-1) signal transduction cascade over the last two decades. Wnt genes encode small secreted proteins that are found in all animal genomes. Wnt signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues.
更多信息
| Molecular Weight | 484.6 g/mol |
|---|---|
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
| Alternative Names | Inhibitor of Wnt Production-3 |
| Cas Number | 687561-60-0 |
| Chemical Formula | C₂₂H₁₇FN₄O₂S₃ |
| Purity | ≥ 98% |
| Target | Porcupine |
| Pathway | WNT |
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