Development of in silico fragment mapping method for discovery of small-molecule PPI inhibitors

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14875
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Kitasato University
• Principal Investigator: Ozawa Shin-ichiro 北里大学, 薬学部, 助教 (20724868)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: インシリコ創薬 / フラグメントベース創薬 / フラグメントマッピング / PPI阻害剤

Outline of Final Research Achievements

Protein-protein interactions (PPIs) are highly involved in most cellular processes, and thus the discovery of PPI inhibitors is considered as a promising therapeutic strategy for several diseases. In this study, we optimized the protocol of our in silico fragment mapping method for the PPI inhibitor searching, and then successfully identified the lead compounds for the development of the inhibitors for several PPI targets. These results demonstrated the utility of our in silico fragment method as a novel computational fragment-based drug design (FBDD) methodology.

Free Research Field

創薬化学

Academic Significance and Societal Importance of the Research Achievements

PPI阻害剤の開発支援を目的とした従来の計算手法の多くは、結合フラグメント予測の際のドッキング計算の精度が問題となっていた。一方で、インシリコ・フラグメントマッピング法はドッキング計算に依らない知識ベースの計算手法であるため、従来法の弱点を補完することが可能となる。本手法の確立により、フラグメント情報に基づく化合物の高速スクリーニングや合理的設計など、高難易度なPPI標的における創薬加速が期待される。