Background
IWR-1-endo is a small molecule inhibitor of Wnt Response with IC50 value of 180nM [1].
IWR-1-endo is a small molecule antagonists of the Wnt/β-catenin pathway screened out from a diverse synthetic chemical library. It acts as an inhibitor of Wnt response. IWR-1-endo can inhibit the activity of Wnt1, 2 and 3. In cultured cells, IWR-1-endo inhibits Wnt-induced β-catenin accumulation which is a downstream event of Lrp6 and Dvl2. It is proved that IWR-1-endo promote β-catenin destruction through promoting stability of Axin-scaffolded destruction complexes in the DLD-1 colorectal cancer (CRC) cell line. IWR-1-endo is also shown to inhibit tailfin regeneration and epithelial stem cell self-renewal in zebrafish. These two processes are both dependent on Wnt/β-catenin signaling. Furthermore, IWR-1-endo can block aberrant cell growth supported by hyperactivation of Wnt/β-catenin resulting from Apc loss [1].
IWR-1-endo是一种Wnt反应的小分子抑制剂，其IC50值为180nM [1]。
IWR-1-endo是从多种合成化学库中筛选出的Wnt/β-catenin途径的小分子拮抗剂。它作为Wnt反应的抑制剂。IWR-1-endo可以抑制Wnt1、2和3的活性。在培养的细胞中，IWR-1-endo抑制了Wnt诱导的β-catenin积累，这是Lrp6和Dvl2的下游事件。证明了IWR-1-endo通过促进DLD-1结直肠癌细胞株中的Axin支架的破坏复合物的稳定性促进β-catenin的破坏。 IWR-1-endo还显示可以抑制斑马鱼的尾鳍再生和上皮干细胞自我更新。这两个过程都依赖于Wnt/β-catenin信号。此外，IWR-1-endo可以阻止由于Apc丧失而导致的Wnt/β-catenin的高度活化支持的异常细胞生长 [1]。
参考文献:
[1] Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan CW, Wei S, Hao W, Kilgore J, Williams NS, Roth MG, Amatruda JF, Chen C, Lum L. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009 Feb;5(2):100-7.
Protocol
| Cell experiment [1]: |
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Cell lines
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DLD-1 colorectal cancer (CRC) cell line
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Preparation method
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The solubility of this compound in DMSO is >20.5mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
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Reacting condition
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1 μM, 2.5 μM, 10 μM
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Applications
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IWR-1-endo promoted β-catenin destruction through promoting stability of Axin-scaffolded destruction complexes in the DLD-1 colorectal cancer (CRC) cell line. IWR-1-endo blocked aberrant cell growth supported by hyperactivation of Wnt/β-catenin resulting from Apc loss.
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| Animal experiment [1]: |
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Animal models
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Zebrafish
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Dosage form
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10 mM, 24 h
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Application
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IWR-1-endo inhibited tailfin regeneration and epithelial stem cell self-renewal in zebrafish.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1]. Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan CW, Wei S, Hao W, Kilgore J, Williams NS, Roth MG, Amatruda JF, Chen C, Lum L. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009 Feb;5(2):100-7.
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