Abstract 5560: Characterization of a new non-steroidal small molecule inhibitor of CYP17 for castration-resistant prostate cancer.

Abstract Prostate cancer affects 1 in 6 men and is the second most common cause of cancer-related death. Since the majority of prostate cancers critically depend on androgens for growth, androgen deprivation therapy is a frontline treatment for advanced prostate cancer. The majority of prostate tumors initially respond to androgen deprivation therapy, but eventually the disease often progresses to castration-resistant prostate cancer. However, the current therapies that only reduce androgen produced in the testis do not affect androgen produced by adrenal glands can also produce androgens. This extra-testicular androgen production is thought to be a key factor in the development of castration resistant prostate cancer. CYP17 is a P450 enzyme that catalyzes the last step of androgen biosynthesis in both the testis and the adrenals. Inhibition of CYP17 therefore completely blocks androgen production and it is thus thought to be more effective to prevent prostate cancer progression than current therapies. Angion Biomedica has identified a promising series of proprietary non-steroidal CYP17 inhibitors. Our lead compound is potent, orally bioavailable, and significantly reduces serum testosterone levels in mice. Treatment of rats and mice with our lead CYP17 inhibitor significantly reduces the weights of androgen dependent organs. In two mouse xenograft models of androgen-dependent tumor growth our lead CYP17 inhibitor markedly reduces primary tumor growth, serum testosterone and PSA levels. Angion is currently further evaluating the therapeutic potential of this series of compounds as a possible therapy for castration resistant prostate cancer. Citation Format: Bert Oehlen, Siobhan McCormack, Gaifeng Ma, Dong Sung Lim, Bijoy Panicker, Itzhak D. Goldberg. Characterization of a new non-steroidal small molecule inhibitor of CYP17 for castration-resistant prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5560. doi:10.1158/1538-7445.AM2013-5560