Development of sunitinib-based molecular targeted drug conjugates

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16325
• 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: Nagoya University
• Principal Investigator: Doura Tomohiro 名古屋大学, 工学研究科, 助教 (00745226)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ケモジェネティクス / リガンド / 受容体 / GPCR

Outline of Final Research Achievements

Although tyrosine kinase inhibitors (TKIs) are known as a class of molecular targeted drugs, the subtype selectivity of TKIs are not very high because TKIs bind to the ATP binding sites which are common structures among receptor tyrosine kinases. In order to improve the selectivity of ligands to the target proteins, I performed the development of ligands which inhibit wild type receptors but not inhibit mutant receptors based on chemogenetics. As the results, I succeeded to discover the chemogenetic ligands for several G protein coupled receptors (GPCRs).

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

リガンドの標的タンパク質への選択性を高めることは、細胞や生物個体のような多様なタンパク質が存在する環境中で特定タンパク質の機能を制御することを可能にするため、脳機能のような複雑な生命機能の解明につながる。また、リガンドの標的タンパク質への選択性の向上は薬の薬物標的への選択性の向上につながるため、創薬の観点からも重要な知見であると言える。