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Development of drug-resistance-overcoming agents targeting histone demethylase JARID1A

Research Project

Project/Area Number 25640093
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionNagahama Institute of Bio-Science and Technology

Principal Investigator

Tamio Mizukami  長浜バイオ大学, バイオサイエンス学部, 教授 (80367896)

Research Collaborator SASAKI Ryuzo  長浜バイオ大学, バイオサイエンス学部, 客員教授 (60077378)
HASEGAWA Makoto  長浜バイオ大学, バイオサイエンス学部, 教授 (10367899)
NAGAI Nobuo  長浜バイオ大学, バイオサイエンス学部, 教授 (90260281)
Wada Shuichi  長浜バイオ大学, バイオサイエンス学部, 准教授 (20378607)
SUZUKI Takayoshi  京都府立医科大学, 医学研究科医薬品化学講座, 教授 (90372838)
MIYATA Naoki  名古屋市立大学, 大学院薬学研究科薬化学分野, 教授 (50114674)
Yoshida Minoru  理化学研究所基幹研究所, 吉田化学遺伝学研究室, 主任研究員 (80191617)
Itoh Akihiro  理化学研究所基幹研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords分子標的治療 / 抗がん剤耐性
Outline of Final Research Achievements

Histone lysine methylation status is well controlled by histone lysine-specific methyltransferases and demethylases. This control plays a crucial role in the epigenetic gene expression and is frequently involved in cell proliferation and survival in cancer. JARID1A is a histone demethylase whose substrates are H3K4me2/me3. JARID1A has been reported as a drug-resistance-causing molecule in 2010; overexpression of JARID1A allowed cancer cells to acquire drug resistance, whereas knockdown of JARID1A expression by RNA interference sensitized drug resistance. These results suggest that JARID1A is an interesting drug discovery target for drug-resistance-overcoming agents. In this study, we attempted to develop JARID1A inhibitors as epigenomic drugs that have drug-resistance-overcoming activity.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (1 results)

All 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Identification of Jumonji AT-Rich Interactive Domain 1A Inhibitors and Their Effect on Cancer Cells.2015

    • Author(s)
      Itoh Y, Sawada H, Suzuki M, Tojo T, Sasaki R, Hasegawa M, Mizukami T, Suzuki T
    • Journal Title

      ACS Med Chem Lett.

      Volume: 6 Issue: 6 Pages: 665-670

    • DOI

      10.1021/acsmedchemlett.5b00083

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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