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Development of a novel anticancer drug targeting UBL-UBA family protein

Research Project

Project/Area Number 20710175
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Living organism molecular science
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

KAWATANI Makoto  The Institute of Physical and Chemical Research, 化合物ライブラリー評価研究チーム, 研究員 (50391925)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsUBL-UBA型ユビキチンレセプター / 阻害剤 / 癌
Research Abstract

The purpose of this study is to develop an anticancer agent targeting UBL-UBA family protein. I found that GUT-70, an antiproliferative compound, binds to ubiquilin 1. GUT-70 accumulated intercellular ubiquitinated proteins, and proteome analysis showed that GUT-70 is classified into the same cluster as a proteasome inhibitor. These results suggest that GUT-70 targets ubiquilin 1, thereby suppressing ubiqutin-proteasome system, resulting in the growth inhibition of cancer cells.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (31 results)

All 2009 2008 Other

All Journal Article (19 results) (of which Peer Reviewed: 12 results) Presentation (10 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases.2009

    • Author(s)
      Kawatani M, Osada H
    • Journal Title

      Cancer Sci. 100

      Pages: 1999-2005

    • NAID

      10027196327

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] グリオキサラーゼI2009

    • Author(s)
      川谷誠
    • Journal Title

      Medical Tribune 42

      Pages: 50-50

    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Journal Article] レドックス制御に干渉する小分子のケミカルバイオロジー2009

    • Author(s)
      川谷誠, 奥村英夫, 長田裕之
    • Journal Title

      実験医学(増刊) 27

      Pages: 218-224

    • Related Report
      2009 Final Research Report
  • [Journal Article] 破骨細胞を標的とする天然低分子化合物のケミカルジェネティクス2009

    • Author(s)
      川谷誠, 長田裕之
    • Journal Title

      細胞工学 28

      Pages: 338-344

    • Related Report
      2009 Final Research Report
  • [Journal Article] 破骨細胞の分化を阻害する小分子化合物2009

    • Author(s)
      川谷誠, 奥村英夫, 長田裕之
    • Journal Title

      バイオサイエンスとインダストリー 67

      Pages: 24-28

    • NAID

      10024745896

    • Related Report
      2009 Final Research Report
  • [Journal Article] Polo-like kinase 1 phosphorylates and regulates Bcl-xL during pironetin-induced apoptosis.2009

    • Author(s)
      Kawatani M (7名中5番目)
    • Journal Title

      Oncogene 28

      Pages: 107-116

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases2009

    • Author(s)
      Kawatani, M., Osada, H.
    • Journal Title

      Cancer Sci. 100

      Pages: 1999-2005

    • NAID

      10027196327

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] レドックス制御に干渉する小分子のケミカルバイオロジー2009

    • Author(s)
      川谷誠, 他
    • Journal Title

      実験医学(増刊) 27

      Pages: 218-224

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 破骨細胞を標的とする天然低分子化合物のケミカルジェネティクス2009

    • Author(s)
      川谷誠, 他
    • Journal Title

      細胞工学 28

      Pages: 338-344

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 破骨細胞の分化を阻害する小分子化合物2009

    • Author(s)
      川谷誠, 他
    • Journal Title

      バイオサイエンスとインダストリー 67

      Pages: 24-28

    • NAID

      10024745896

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Polo-like kinase 1 phosphorylates and regulates Bcl-xL during pironetin induced apoptosis2009

    • Author(s)
      Tamura Y., et al.
    • Journal Title

      Oncogene 28

      Pages: 107-116

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Robust and systematic drug screening method using chemical arrays and the protein library: identification of novel inhibitors of carbonic anhydrase II.2008

    • Author(s)
      Kawatani M (5名中4番目)
    • Journal Title

      Biosci. Biotechnol. Biochem. 72

      Pages: 2739-2749

    • NAID

      10027533381

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I.2008

    • Author(s)
      Kawatani M (11名中1番目)
    • Journal Title

      Proc. Natl. Acad. Sci. USA 105

      Pages: 11691-11696

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and biological activities of reveromycin A and spirofungin A derivatives.2008

    • Author(s)
      Kawatani M (10名中4番目)
    • Journal Title

      Bioorg. Med. Chem. Lett. 18

      Pages: 3756-3760

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Robust and systematic drug screening method using chemical arrays and the protein library : identification of novel inhibitors of carbonic anhydrase II2008

    • Author(s)
      Miyazaki I., et al.
    • Journal Title

      Biosci. Biotechnol. Biochem. 72

      Pages: 2739-2749

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I2008

    • Author(s)
      Kawatani M., et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 105

      Pages: 11691-11696

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and biological activities of reveromycin A and spirofungin A derivatives2008

    • Author(s)
      Shimizu T., et al.
    • Journal Title

      Bioorg. Med. Chem. Lett. 18

      Pages: 3756-3760

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in hypoxic environment.

    • Author(s)
      Kawatani M (16名中5番目)
    • Journal Title

      Cell Death Diff. (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glyoxalase-I is a novel target against Bcr-Abl^+ leukemic cells acquiring stem-like characteristics in hypoxic environment

    • Author(s)
      Takeuchi, M.et al.
    • Journal Title

      Cell Death Diff. (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of a novel DNA topoisomerase II inhibitor by proteomic profiling2009

    • Author(s)
      川谷誠
    • Organizer
      AACR-NCI-EORTC International Conference "Molecular Targets and Cancer Therapeutics"
    • Place of Presentation
      ボストン
    • Related Report
      2009 Final Research Report
  • [Presentation] Methyl gerfelin, a small molecule inhibitor of osteoclastogenesis that acts via inhibition of glyoxalase I2009

    • Author(s)
      川谷誠
    • Organizer
      The 26th Naito Conference-Osteobiology-
    • Place of Presentation
      淡路島
    • Related Report
      2009 Final Research Report
  • [Presentation] 分化誘導活性物質NPD723の作用機構解析2009

    • Author(s)
      川谷誠
    • Organizer
      第13回日本がん分子標的治療学会学術集会
    • Place of Presentation
      徳島
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Identification of a novel DNA topoisomerase II inhibitor by proteomic profiling2009

    • Author(s)
      川谷誠 et al.
    • Organizer
      AACR-NCI-EORTC International Conference "Molecular Targets and Cancer Therapeutics"
    • Place of Presentation
      Boston
    • Related Report
      2009 Annual Research Report
  • [Presentation] Methyl gerfelin, a small molecule inhibitor of osteoclastogenesis that acts via inhibition of glyoxalase I2009

    • Author(s)
      川谷誠 et al.
    • Organizer
      The 26^<th> Naito Conference-Osteobiology-
    • Place of Presentation
      淡路島
    • Related Report
      2009 Annual Research Report
  • [Presentation] Screening and target identification of bioprobes2008

    • Author(s)
      川谷誠
    • Organizer
      第1回理研ケミカルバイオロジー研究領域国際シンポジウム
    • Place of Presentation
      熱海
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] 抗腫瘍活性物質GUT-70の作用機構解析2008

    • Author(s)
      川谷誠
    • Organizer
      第12回がん分子標的治療研究会総会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] The identification of a novel inhibitor of osteoclastogenesis that acts via inhibition of glyoxalase I2008

    • Author(s)
      川谷誠
    • Organizer
      第4回日韓合同シンポジウム
    • Place of Presentation
      日光
    • Related Report
      2009 Final Research Report
  • [Presentation] 抗腫瘍活性物質BNS-22はDNA topoisomerase II活性を阻害する2008

    • Author(s)
      川谷誠
    • Organizer
      日本ケミカルバイオロジー研究会第3回年会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] The identification of a novel inhibitor of osteoclastogenesis that acts via inhibition of glyoxalase I2008

    • Author(s)
      川谷誠, 他
    • Organizer
      第4回日韓合同シンポジウム
    • Place of Presentation
      日光
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規ユビキリン結合性小分子2008

    • Inventor(s)
      長田裕之、川谷誠、木村晋也、前川平、水戸潤
    • Industrial Property Rights Holder
      理化学研究所、京都大学
    • Filing Date
      2008-05-02
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 新規ユビキリン結合性小分子2008

    • Inventor(s)
      長田裕之, 他
    • Industrial Property Rights Holder
      理化学研究所・京都大学
    • Filing Date
      2008-05-02
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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