Design and synthesis of acetylglucose-modified dasatinib and evaluation of radiosensitizing effect

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07567
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: The University of Tokushima
• Principal Investigator: UTO Yoshihiro 徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 教授 (20304553)
• Co-Investigator(Kenkyū-buntansha): 山田 久嗣 徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 准教授 (80512764)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 放射線増感剤

Outline of Final Research Achievements

In this study, we designed and synthesized a derivative of the anticancer drug dasatinib modified with acetyl glucose, clarified its antitumor activity and radiosensitizing activity, and demonstrated its usefulness as a radiosensitizer using a tumor-implanted chicken egg model. As a summary of the research results, we succeeded in molecular design and synthesis of dasatinib derivative UTX-136 modified with acetyl glucose, which has significantly higher radiosensitizing effect than dasatinib, and which is degraded inside and outside tumor cells to produce dasatinib. It was revealed that it has a higher glucose uptake inhibitory ability than dasatinib, and that it is taken up into tumors in a tumor-implanted chicken egg model.

Free Research Field

創薬化学

Academic Significance and Societal Importance of the Research Achievements

国内外の放射線増感剤の開発については，国内では過酸化水素(オキシドール)を主成分とした放射線治療用増感剤KORTUC，国外ではニモラゾールが成功例として挙げられるが，対象疾患が限定されるため新たな放射線増感剤の開発が急務である．本研究成果は、承認済の分子標的薬にアセチルグルコースを導入することで放射線増感活性を付与し，分子標的薬そのものの薬物動態や抗癌活性への影響を最小限にして臨床利用が可能な放射線増感剤を創出するものであり，承認済の薬剤を利用するため製薬企業による放射線増感剤の開発を容易にするとともに，臨床の現場で抗癌剤と同様に利用できることが期待できるため学術的・社会的意義は大きい。