Development of an Easily Modifiable Compound Library with More Complex Three-Dimensional Structures
| Project/Area Number |
16K18912
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Kitasato University |
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Principal Investigator |
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 創薬化学 / ライブラリー構築 / click反応 / 医薬分子設計 / 立体的ファーマコフォア / 化合物ライブラリー |
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| Outline of Final Research Achievements |
Ligands, small molecules that bind to the target proteins, are indispensable in drug development. Despite this, it is difficult to find out a ligand for proteins whose ligands have not ever been discovered. To address this issue, we set out to construct a compound library with high expectancy of discovering novel ligands.
It is currently said that sterically more complex molecules are more advantageous in developing drugs. Hence, we constructed a compound library by modifying a three-dimensional 7-azanorbornane scaffold. By screening through the library constructed in this way, we successfully identified novel ligands for growth hormone secretagogue receptor and opioid receptors.
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| Academic Significance and Societal Importance of the Research Achievements |
既知のリガンドが存在しないタンパク質を創薬の標的とする場合, 膨大な数 (数十万程度)の化合物の中からリガンドを探し出すハイスループットスクリーニングと呼ばれる方法を取ることが多い. しかし, ハイスループットスクリーニングでリガンドを見つけられる確率は一般的に非常に低く, このことが医薬開発の遅れを招いている可能性がある. これに対して, 本研究でとった手法では, 23% (22化合物中5化合物)という非常に高い確率で, リガンドとなる化合物を見つけることができた. この手法により, 将来的には, 新たに発見されたタンパク質を標的とした創薬が容易になることが期待される.
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Report
(4 results)
Research Products
(6 results)
