2019 Fiscal Year Final Research Report
Development of anticancer lead based on catalytic asymmetric total synthesis of leucinostatin A
| Project/Area Number |
17K08384
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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 |
Drug development chemistry
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| Research Institution | Microbial Chemistry Research Foundation |
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Principal Investigator |
Watanabe Takumi 公益財団法人微生物化学研究会, 微生物化学研究所, 部長 (80270544)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | ロイシノスタチン / がんー間質相互作用 / 医薬化学 / 構造活性相関 / ペプチド / 天然物 / 分子標的薬 |
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| Outline of Final Research Achievements |
Currently available targeted therapy of tumor acts on growth signal within tumor cells, which realizes potent and selective anti-tumor activity, and is clinically successful indeed. However,genetic instability of tumor cells frequently cause resistance toward this type of therapy. Based on this background, growth signals from normal cells (stromal cells) neighboring tumor cells are recognized as good candidate of molecular target of future anti-cancer medicine.
Leucinostatin A acts on this cross-talk of tumor and stromal cells to inhibit proliferation of the tumor cells.In this study, leucinostatin and related compounds were found to inhibit complex V, a key enzyme in mitochondrial respiratory chain, to reduce expression of IGF-I. in fact, these compounds supressed growth of tumor cells, showed and anti-tumor activity in model mice.
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| Free Research Field |
医薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
がんとの闘いにおいて人類は様々な効果的治療法を開発してきたが，いずれも長所と短所を併せ持ち，新たな選択肢も常に待ち望まれている．低分子創薬の分野ではがん細胞に対する高選択性を特長とする分子標的薬に高頻度の耐性発現が知られる．本研究ではがん組織中のがん細胞の周囲に存在する、間質細胞とよばれる正常細胞がもつミトコンドリア呼吸鎖関連酵素・complex Vを新たな抗がん剤分子標的として提示するに至った．正常細胞の遺伝子の安定性に鑑み，耐性の発現し難い抗がん剤開発の基礎的知見としての意義をもつ．
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