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EPHX2 phosphatase as a novel target of drug discovery: searches for a physiologically relevant substrate and a specific inhibitor

Research Project

Project/Area Number 17H02201
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

Hasumi Keiji  東京農工大学, (連合)農学研究科(研究院), 教授 (20208474)

Co-Investigator(Kenkyū-buntansha) 鈴木 絵里子  東京農工大学, (連合)農学研究科(研究院), 講師 (00468513)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywords炎症 / 可溶性エポキシドヒドロラーゼ / 生理活性脂質 / 阻害剤 / Epoxide hydrolase / Inhibitor / Substrate / Lipid mediator / substrate / 生体分子科学 / 生理活性物質
Outline of Final Research Achievements

Soluble epoxide hydrolase is a bifunctional enzyme that has an N-terminal phosphatase and C-terminal epoxide hydrolase. Although many of the anti-inflammatory phenotypes have been believed to be derived from C-EH regulation, we found a definitive role of N-phos in the regulation of vascular inflammation and hepatic steatosis. Moreover, we identified phosphatidic acids with a long-chain polyunsaturated fatty acid at the sn-2 position as a substrate for N-phos, utilizing a newly developed LC-MS/MS method combined with an isotope-labeled tagging.

Academic Significance and Societal Importance of the Research Achievements

炎症は組織傷害などの治癒に必須の過程であり、生体機能の維持に必須である一方で、慢性炎症は脳梗塞、心筋梗塞、肥満・糖尿病、腎臓病などの多くの重篤な病態の基礎疾患となる。それゆえその制御は健康な生活の維持に極めて重要である。従来の炎症制御に関する膨大な試みの結果多くの医薬品が開発されてきたが、それでもなお多くの重篤かつ難治性の炎症性疾患が残されており、その治療法の開発が待望されている。本研究の成果はその開発に資する新たな化合物と標的分子を提供するものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (7 results)

All 2019 2017 Other

All Int'l Joint Research (3 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] University of California Davis(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of California Davis(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of California - Davis/Department of Entomology/UCD Comprehensive Cancer Center(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] N-Substituted amino acid inhibitors of the phosphatase domain of the soluble epoxide hydrolase2019

    • Author(s)
      Naoki Matsumoto, Masaki Kataoka, Hibiki Hirosaki, Christophe Morisseau, Bruce D. Hammock, Eriko Suzuki, and Keiji Hasumi
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 未定

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Regulation of vascular inflammation and liver defense system by a lipid substrate of N-terminal phosphatase of soluble epoxide hydrolase2019

    • Author(s)
      E. Suzuki, H. Hirosaki, M. Tajima, M. Nakano, H. Kinoshita, J. Abe, K. Hasumi
    • Organizer
      27th Congress of the International Society of Thrombosis and Haemostasis
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生理活性物質SMTPによる血管炎症制御:beta-2アドレナリン受容体―IL-6シグナル経路の関与2019

    • Author(s)
      鈴木絵里子、田島真梨絵、中野真衣、廣嵜響、木下春奈、蓮見惠司
    • Organizer
      第41回日本血栓止血学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 可溶性エポキシドハイドロラーゼN末端phosphataseの生体内基質探索および機能解析2017

    • Author(s)
      廣嵜響、田島真梨絵、悴田正浩、阿部純己、中野真衣、松本直欣、鈴木絵里子、蓮見惠司
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-05-20  

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