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Elucidation of the action mechanism of Wnt pathway inhibitors by vertebrate chemical genetics

Research Project

Project/Area Number 22790082
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionIwate Medical University

Principal Investigator

NISHIYA Naoyuki  岩手医科大学, 薬学部, 講師 (10286867)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords癌 / シグナル伝達 / 細胞・組織 / 発生・分化 / 薬学分子生物学 / 再生医学 / 薬学
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.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 2010

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (18 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Journal Article] Identification of LY83583 as a specific inhibitor of Candida albicans MPS1 protein kinase2011

    • Author(s)
      Tsuda K, Nishiya N, Umeyama T and Uehara Y.
    • Journal Title

      Biochem. Biophys. Res . Commun

      Volume: 409 Pages: 418-423

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] 上原至雅Wnt/β-catenin経路阻害活性をもつGGTI-286の作用機序の解析2013

    • Author(s)
      大森紀和、阿部早織、岩岡ささの、大西亨美、佐々木朱里、庄司桃子、奥 裕介、西谷直之
    • Organizer
      日本薬学会 第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] がん細胞と微小環境との相互作用の薬理学的制御2013

    • Author(s)
      上原至雅、奥 裕介、西谷直之
    • Organizer
      日本農芸化学会2013年度大会シンポジウム「細胞骨格とシグナル伝達の理解からがんに迫る」
    • Place of Presentation
      仙台
    • Year and Date
      2013-03-27
    • Related Report
      2012 Final Research Report
  • [Presentation] がん細胞と微小環境との相互作用の薬理学的制御2013

    • Author(s)
      上原至雅
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Wnt/β-catenin経路阻害活性をもつGGTI-286の作用機序の解析2013

    • Author(s)
      大森紀和
    • Organizer
      第132年会日本薬学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Rho-associated coiled coil kinase (ROCK)阻害剤による染色体不安定性の誘導2013

    • Author(s)
      垂柳智秋
    • Organizer
      第132年会日本薬学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Geranylgeranyltransferase inhibitors attenuate the Wnt/beta-catenin signaling pathway.2013

    • Author(s)
      Nishiya, N.
    • Organizer
      FAOBMB mini symposium 2013
    • Place of Presentation
      矢巾
    • Related Report
      2012 Annual Research Report
  • [Presentation] ROCK-LIMK1 axis activates Aurora A and participates in centrosome integrity。2013

    • Author(s)
      Oku, Y.
    • Organizer
      FAOBMB mini symposium 2013
    • Place of Presentation
      矢巾
    • Related Report
      2012 Annual Research Report
  • [Presentation] IMU14 derivatives as novel Wnt/ β-catenin signaling inhibitors2012

    • Author(s)
      Nishiya, N., Kawano, T., Uehara、Y.
    • Organizer
      日本癌学会 第71回総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] タンパク質の脂質修飾制御による選択的Wnt/ β-cateninシグナル阻害2012

    • Author(s)
      西谷直之、奥 裕介、上原至雅
    • Organizer
      第16回日本がん分子標的治療学会学術集会
    • Place of Presentation
      北九州
    • Year and Date
      2012-06-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規Wnt/β-cateninシグナル阻害剤IMU1003の同定2012

    • Author(s)
      小松豊徳、三田地沙織、河野富一、西谷直之、上原至雅
    • Organizer
      日本薬学会 第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 上原至雅ゼブラフィッシュ胚を用いたWnt/β-catenin 経路阻害剤探索系の構築2012

    • Author(s)
      山口英美、熊谷裕介、佐藤佑樹、西谷直之
    • Organizer
      日本薬学会 第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] ゼブラフィッシュ胚を用いたWnt/β-catenin経路阻害剤探索系の構築2012

    • Author(s)
      山口英美、熊谷裕介、佐藤佑樹、西谷直之、上原至雅
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規Wnt/β-cateninシグナル阻害剤IMU1003の同定2012

    • Author(s)
      小松豊徳、三田地沙織、河野富一、西谷直之、上原至雅
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] タンパク質の脂質修飾制御による選択的Wnt/β-cateninシグナル阻害2012

    • Author(s)
      西谷直之
    • Organizer
      第16回日本がん分子標的治療学会学術集会
    • Place of Presentation
      北九州
    • Related Report
      2012 Annual Research Report
  • [Presentation] IMU14 derivatives as novel Wnt/beta-catenin signaling inhibitors.2012

    • Author(s)
      西谷直之
    • Organizer
      日本癌学会 第71回総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] ゼブラフィッシュ胚を用いたWnt/β-カテニンシグナル阻害剤の探索2011

    • Author(s)
      西谷直之、河野富一、津田香代子、上原至雅
    • Organizer
      日本がん分子標的治療学会第15回学術集会
    • Place of Presentation
      台場
    • Year and Date
      2011-06-23
    • Related Report
      2012 Final Research Report
  • [Presentation] ゼブラフィッシュ胚を用いたWnt/β-cateninシグナル阻害剤の探索2011

    • Author(s)
      西谷直之、河野富一、津田香代子、上原至雅
    • Organizer
      日本がん分子標的治療学会第15回学術集会
    • Place of Presentation
      台場
    • Year and Date
      2011-06-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] ゲフィチニブ耐性EGFR T790M変異の克服を志向したキナーゼ阻害剤プロファイリング2010

    • Author(s)
      西谷直之、津田香代子、上原至雅
    • Organizer
      日本がん分子標的治療学会 第14回学術集会
    • Place of Presentation
      江戸川区船堀
    • Year and Date
      2010-07-08
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 胚の発生および/または分化を制御する方法2012

    • Inventor(s)
      西谷直之 、河野富一、 畠中 稔、 上原至雅
    • Industrial Property Rights Holder
      西谷直之 、河野富一、 畠中 稔、 上原至雅
    • Filing Date
      2012-03-14
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 胚の発生および/または分化を制御する方法2012

    • Inventor(s)
      西谷直之、河野富一、畠中稔、上原至雅
    • Industrial Property Rights Holder
      西谷直之、河野富一、畠中稔、上原至雅
    • Filing Date
      2012-03-14
    • Related Report
      2011 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 胚の発生および/または分化を制御する方法2011

    • Inventor(s)
      西谷直之 、河野富一、 畠中 稔、上原至雅
    • Industrial Property Rights Holder
      西谷直之 、河野富一、 畠中 稔、上原至雅
    • Industrial Property Number
      2011-041262
    • Filing Date
      2011-02-28
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 胚の発生および/または分化を制御する方法2011

    • Inventor(s)
      西谷直之、河野富一、畠中稔、上原至雅
    • Industrial Property Rights Holder
      西谷直之、河野富一、畠中稔、上原至雅
    • Industrial Property Number
      2011-041262
    • Filing Date
      2011-02-28
    • Related Report
      2011 Annual Research Report 2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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