2021 Fiscal Year Final Research Report
The development of Glyoxalase I inhibitors as novel cancer therapeutics by in silico methods
| Project/Area Number |
19K05737
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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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| Review Section |
Basic Section 37030:Chemical biology-related
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Takasawa Ryoko 東京理科大学, 薬学部薬学科, 准教授 (10398828)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Glyoxalase I / がん特異的代謝 / 制がん剤リード化合物 / in silicoスクリーニング |
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| Outline of Final Research Achievements |
The purpose of this study is to create novel inhibitors of Glyoxalase I (GLO I), which is highly expressed specifically in cancer cells, as lead compounds for anticancer agents. In this study, we analyzed the X-ray crystal structure of the complex of the human GLO I and the novel GLO I inhibitor compound TLSC702, which found in our laboratory, and succeeded in elucidating the binding mode of TLSC702 to human GLO I. Furthermore, we discovered several GLO I-inhibiting natural organic compounds. This study is an important milestone for our designing of the novel human GLO I inhibitors and the data are very significant and useful in the creation of the lead compounds for the development of novel molecular-targeted drugs for cancer therapy that inhibit GLO I enzymatic activity.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は，AI創薬によるGLO I阻害剤の構造最適化を目指している．本研究で得られたTLSC702とGLO Iの結合様式データを用いることで，AI創薬による阻害剤の構造最適化設計が可能となる．また，新たに見出したGLO I阻害天然有機化合物の構造活性相関解析のデータもAI創薬に利用できる．これに基づいてAI創薬，有機合成展開，その実測評価のフィードバックによる最適化プロセスを実行することで迅速に新薬リード化合物にたどりつくことが可能となると考えている．本研究は，AI創薬を駆使した最適医薬分子創製の新たな道を切り拓き，ひいては真のテーラーメイド医療の実現に大きく貢献することになると期待できる．
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