2012 Fiscal Year Final Research Report
Elucidation of the action mechanism of Wnt pathway inhibitors by vertebrate chemical genetics
Project/Area Number |
22790082
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Biological pharmacy
|
Research Institution | Iwate Medical University |
Principal Investigator |
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Project Period (FY) |
2010 – 2012
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Keywords | 癌 / シグナル伝達 / 細胞・組織 / 発生・分化 / 薬学分子生物学 |
Research Abstract |
The evolutionarily conserved Wnt/β-catenin pathway is crucial for normal embryogenesis as well as abnormal activation observed in tumors such as colorectal cancers. We identified a low molecular weight compound IMU14 and its derivatives as novel Wnt/ β-catenin pathway inhibitors through an unconventionalvertebrate in vivo screening system, in which effects of test compounds on zebrafish embryogenesis was evaluated. In this study, we aimed to elucidate the action mechanism of the IMU compounds. An immobilized IMU compound co-precipitated a protein complex containing β-catenin and GSK-3β. Furthermore, chemical genetics showed functional interaction between a target molecule of the IMU compounds and GSK-3β.
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