Development of novel anti-cancer agents targeting de novo pyrimidine biosynthetic pathway

2015 Fiscal Year Final Research Report

• Project/Area Number: 25350981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kawatani Makoto 国立研究開発法人理化学研究所, 環境資源科学研究センター, 専任研究員 (50391925)
• Research Collaborator: OKUMURA Hideo 公益財団法人高輝度光科学研究センター, タンパク質結晶解析推進室, 研究員 (90377903) ; SHIMIZU Takeshi 国立研究開発法人理化学研究所, 環境資源科学研究センター, 嘱託職員 ; HIRANUMA Sayoko 国立研究開発法人理化学研究所, 環境資源科学研究センター, 嘱託職員 ; WIERZBA Konstanty 国立研究開発法人理化学研究所, 環境資源科学研究センター, 嘱託職員
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: がん / 抗がん剤

Outline of Final Research Achievements

The purpose of this study is to develop novel anti-cancer agents targeting de novo pyrimidine biosynthetic pathway based on our recently-discovered DI-01 compound. DI-01 strongly inhibited cell proliferation in a wide variety of human cancer cell lines, and showed a marked synergistic effect when used with 5-fluorouracil (5-FU). Although DI-01 was poorly-soluble and metabolically unstable, we successfully developed DI-148 with a good pharmacokinetic profile by a series of structure optimization.

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