| Project/Area Number |
15K07865
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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 pharmacy
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
KATOH Tadashi 東北医科薬科大学, 薬学部, 教授 (50382669)
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| Co-Investigator(Kenkyū-buntansha) |
成田 紘一 東北医科薬科大学, 薬学部, 助教 (20584460)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 分子標的治療薬 / 天然物合成 / 構造活性相関 / TAN-1813 / リファガール / ナキジノール / サルビアミン / タイランデプシン / 抗腫瘍活性物質 / 分子標的抗がん剤 / 天然物創薬 / がん分子標的治療薬 / テルペノイド / 全合成 |
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| Outline of Final Research Achievements |
TAN-1813, which exhibits a prominent p21ras farnesyltransferase inhibitory activity, has been expected to be a novel molecular target anticancer agent. In this research project, the synthesis of the key precursor of TAN-1813 possessing the whole skeleton, asymmetric carbons, and functional groups has been achieved. The synthesis and biological evaluation of liphagal analogues were also achieved, which led to the discovery of promising candidates for novel molecular target anticancer agents; the patent application and paper publication were successfully made. As a second order effect, the total syntheses of nakijinols, salviamines, and thailandepsins were achieved, and a method for industrial producing the key intermediates of macrocyclic depsipeptides was also developed; the patent application, conference presentation, and paper publication were performed.
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| Academic Significance and Societal Importance of the Research Achievements |
がんの薬物療法は、分子標的薬の登場により目覚ましい進歩を遂げているが、いまだ克服できない難治性がんは数多く存在し、より治療効果の高い「新しい分子標的抗がん剤」の開発が切望されている。
本研究では優れた抗腫瘍活性を示すにも関わらず、特異で複雑な化学構造ゆえに合成研究/構造活性相関研究が十分に行われていない生物活性天然物を標的化合物として取り上げ、実践的な全合成ルートの開発を行った。本研究成果は「新しい分子標的抗がん剤開発」への道を拓くものであり、我が国の創薬研究の活性化/製薬産業の発展に寄与することが期待できる。
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