EPHX2 phosphatase as a novel target of drug discovery: searches for a physiologically relevant substrate and a specific inhibitor
| Project/Area Number |
17H02201
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
Hasumi Keiji 東京農工大学, (連合)農学研究科(研究院), 教授 (20208474)
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| 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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(7 results)
