Development of a next-generation platinum-based drug with a markedly high and long-lasting antitumor efficacy

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: Komeda Seiji 鈴鹿医療科学大学, 薬学部, 教授 (60425056)
• Co-Investigator(Kenkyū-buntansha): 平本 恵一 鈴鹿医療科学大学, 薬学部, 助教 (90251793) ; 古川 絢子 鈴鹿医療科学大学, 薬学部, 助教 (10455537) ; 植村 雅子 鈴鹿医療科学大学, 薬学部, 助教 (70511997)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: シスプラチン / 白金製剤 / DNA / 免疫 / 白金錯体

Outline of Final Research Achievements

We presumed that SK36, the lead compound of tetrazolato-brdged complexes, might have an immunostimulatory effect similar to oxaliplatin, in addition to its cell-killing effect targeting DNA. We monitored antitumor efficacy by administration of oxaliplatin and SK36 on C26 colon cancer transplanted immunocompetent mice and immunodeficient mice. As a result, significant suppression of tumor growth was observed by administration of SK36 and oxaliplatin in the immunocompetent mouse group. On the other hand, administration of these drugs to immunodeficient mice did not suppress tumor-growth, and there was no significant difference in tumor volume from the control group. Therefore, it was suggested that the tumor-growth inhibition of SK36 and oxaliplatin is related to their immunostimulatory effects.The antitumor efficacy of SK36 was fouond to be much higher than oxaliplatin, confirming that the tetrazolate bridged complexes are promising candidate for next-generation platinum-based drugs.

Free Research Field

無機医薬品化学

Academic Significance and Societal Importance of the Research Achievements

本研究は、単なる白金製剤類似化合物を合成して薬効を評価するだけの創薬研究ではなく、「型破りな」白金錯体の特性を有効利用し、大幅な薬効の向上と副作用の軽減および作用機序の解明を目的とするものである。研究代表者らによる実験結果から提案された免疫賦活作用は、がん治療に極めて重要な役割を担っており、この免疫賦活作用機序の詳細を明らかにすることで、本医薬品開発研究が加速するのはもちろんのこと、免疫を利用した新たな創薬研究の発展に繋がると考えている。