| Project/Area Number |
16K08327
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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 | Tokyo University of Science |
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Principal Investigator |
Tanuma Sei-ichi 東京理科大学, 研究推進機構総合研究院, 教授 (10142449)
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| Co-Investigator(Kenkyū-buntansha) |
高澤 涼子 東京理科大学, 薬学部薬学科, 講師 (10398828)
佐藤 聡 東京理科大学, 薬学部薬学科, 講師 (40530663)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 癌 / Met / チロシンキナーゼ / キナーゼ阻害剤 / in silico分子設計 / ペプチド / アポトーシス / アロステリック効果 / 薬学 / 制癌剤 / 分子設計 |
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| Outline of Final Research Achievements |
c-Met kinase, an oncogenic c-Met gene product, is known to involved in the many step of cancer growth and development. We have previously found an inhibitory protein against c-Met kinase, and revealed it to bind to the allosteric site of c-Met kinase. Furthermore, the mimetic inhibitory peptide (Vpep) was designed. By the in silico analysis of the binding mode of Vpep in c-Met, we could design Vpep mimetic small molecules (Ai : Allosteric inhibitor) by our COSMOS method. Interestingly, among them, Ai1 was found to enhance the inhibitory activities of c-Met catalytic inhibitors (Ci).
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| Academic Significance and Societal Importance of the Research Achievements |
分子標的抗癌治療薬として、これまで腫瘍特異的なKinaseの活性を阻害するものが多く開発されてきた。しかし、そのほとんどはATP結合(Catalytic)部位への結合活性に有しており、他のKinasesへの影響を低減することは困難であった。c-Met Allosteric部位を標的とした本研究は、極めて新規性及び独創性に富んでおり、学術的にも社会的にも重要な意義を持つと考えられる。
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