Exploration of small molecules that target cancer specific metabolism
| Project/Area Number |
17K01970
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Futamura Yushi 国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (70525857)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | がん代謝 / 微小環境 / ケミカルバイオロジー / がん微小環境 |
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| Outline of Final Research Achievements |
Cancer cells can reprogram their metabolic machinery to survive. This altered metabolism, which is distinct from the metabolism of normal cells, is thought to be a possible target for the development of new cancer therapies. In this study, we classified various cancer cell lines in terms of the metabolic profiles, and constructed a screening system using specific cell lines and Flux analyzer that can monitor bioenergetic profiles (specifically oxygen consumption rate and extracellular acidification rate). Thus, small molecules that target cancer-specific metabolism were investigated. We screened the chemical library of RIKEN NPDepo and found several mitochondrial respiration inhibitors. Furthermore, we developed an in vitro reconstitution assay method for mitochondrial electron transport chain using semi-intact cells with specific substrates for each complex of the mitochondrial electron transport chain and detailed the mechanisms of action of hit compounds.
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| Academic Significance and Societal Importance of the Research Achievements |
本分野では、培養細胞を使った適切なモデル系がなかったこと、また伝統的な酸素分極を用いた解析手法はスループットが低いこと、から探索研究が進んでいなかった。本研究でがん微小環境の解析に適した細胞株を選定し、フラックスアナライザーを用いた評価系を構築したことは、従来の問題を克服し、学術的なインパクトは大きかった。また見出した代謝阻害物質を新しい治療薬開発に繋げることが重要な社会的意義であり、今後も研究開発に精進したい。
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Report
(4 results)
Research Products
(16 results)
