Elucidation of androgen-dependent growth inhibition mechanism in prostate cancer of novel small molecule compound APA

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10615
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: YAMAZAKI Yohko 公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 研究員 (80342690)
• Co-Investigator(Renkei-kenkyūsha): MOMOSE Isao 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 主席研究員 (10270547) ; ABE Hikaru 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (10462269)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 前立腺がん / アンドロゲンレセプター

Outline of Final Research Achievements

Although endocrine therapy is the mainstay of treatment for advanced prostate cancer, most patients with prostate cancer progress from androgen-dependent to castration-resistant (CRPC) disease. Androgen receptor (AR) is required for CRPC progression, but AR inhibitors are antagonists only.
We discovered androprostamine (APA) , a novel inhibitor of androgen-dependent human prostate cancer cell growth, from microbial metabolite. APA showed better antitumor activity than clinically used bicalutamide in in vivo experiments using mice, but side effects such as weight loss were observed. Therefore, we synthesized 50 kinds of derivatives based on APA and succeeded in synthesis of new derivatives which keep antitumor activity with reduced side effects.

Free Research Field

創薬化学