JBIR-120: a new growth inhibitor of hormone-refractory prostate cancer cells

The Journal of Antibiotics
2012.0

Abstract

Prostate cancer is a common nondermatological cancer in older adult men. Androgen receptor (AR) signaling has a central role in prostate cancer cell growth and survival,1 and therefore, androgen ablation therapy is recognized as a standard regimen for the treatment of advanced and metastatic prostate cancers.2 However, most patients who undergo androgen ablation progress from being androgen-dependent to developing hormone-refractory prostate cancer within 2 years after initiating therapy. Although the recurrent tumors are often resistant to standard AR-targeting agents, which cause deprivation of androgens or block androgen–AR interaction, AR-mediated signaling still has a key role in the development and maintenance of hormone-refractory prostate cancers.3–5 Thus, identifying new therapeutic agents targeting the AR signaling pathway may possibly control the occurrence of hormone-refractory prostate cancers. Mashima et al. 6 earlier reported that nigericin can block AR-mediated signaling in hormone-refractory prostate cancer cells. In the current study, we discovered a novel compound—JBIR-120 (1)—extracted from the culture broth of a new Streptomyces strain, RI104-LiC104. This paper describes the isolation, structure elucidation and biological activity of 1.

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