Development of covalent drugs activatable by the target enzymes
| Project/Area Number |
18K14356
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 37030:Chemical biology-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 共有結合医薬 / 標的選択制 / 抗ウイルス薬 / 抗ガン薬 / 核酸誘導体 / 標的選択性 / 核酸アナログ / ポリメラーゼ / 選択性 / 不可逆阻害 |
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| Outline of Final Research Achievements |
A covalent drug is a drug molecule that forms a covalent bond with a target enzyme to inhibit its function, and has high inhibitory activity. Due to this property, covalent drugs targeting various enzymes have been developed in recent years. However, covalent drugs often form covalent bonds with non-targeting proteins, and side effects derived from them are a major issue in the development of covalent drugs. In this research, as a strategy to avoid such side effect problems, we developed a covalent drug that is activated by a target enzyme and developed an antiviral drug by using a nucleoside analog as an example. The developed nucleoside analog showed good pharmacological activity against HIV.
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| Academic Significance and Societal Importance of the Research Achievements |
昨今のコロナウイルス感染症拡大でも明らかになった通り、新規の作用機序と強力な薬理活性を有する抗ウイルス薬の開発は、社会的にも重要な課題である。本研究では一般的に強力な活性を有する共有結合医薬の範疇で、新規の作用機序を有する抗ウイルス薬の開発を行った。医薬開発戦略の特徴は、医薬分子が標的とする酵素に作用した際に初めて、共有結合医薬としての反応性を獲得する点にある。開発した核酸アナログはエイズウイルス(HIV)に対して良好な薬理活性を示した。今後さらなる分子最適化を通じ、さまざま抗ウイルス薬開発に適用可能な方法論としての確立を目指す。
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Report
(3 results)
Research Products
(11 results)
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[Presentation] Development of phosphorofluoridate prodrugs2020
Author(s)
吉田祐希, Zheng Ti, 伏原大地 , 新美結士, 中本航介, 橋谷文貴, 木村康明, 日吉貴子, 齋木由利子, 堀井明, 鈴木哲朗, 村上優子, 阿部 洋
Organizer
日本薬学会第140年会
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