Antarlides F-H, new members of the antarlide family produced by Streptomyces sp. BB47

Shun Saito, Takahiro Fujimaki, Watanalai Panbangred, Ryuichi Sawa, Yasuhiro Igarashi, Masaya Imoto

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Castration-resistant prostate cancer (CRPC) is the most aggressive form of this disease. CRPC remains dependent on androgen receptor (AR) signaling. Therefore, a novel AR antagonist, enzalutamide, is used clinically for the treatment of men with metastatic CRPC. However, enzalutamide-resistant AR has appeared, and a new type of AR antagonist is desired. Previously, in the course of screening for a new type of AR antagonist, we isolated a series of compounds, designated antarlides A-E, that share a novel 22-membered-ring macrocyclic structure and are produced by Streptomyces sp. BB47. In the present study, we found that this strain also produces antarlides F-H as minor components. Antarlide F is a novel geometric isomer of known antarlides. On the other hand, antarlides G and H are new members of the antarlide family that have a 20-membered-ring macrocyclic structure. Antarlides G and H inhibited the binding of androgen to AR in vitro at concentrations similar to those observed with antarlides A-E. In addition, antarlide G inhibited the transcriptional activity of not only wild-type AR but also enzalutamide-resistant AR, suggesting that antarlides with either 22- or 20-membered rings may serve as potent third-generation AR antagonists capable of overcoming resistance to enzalutamide.

Original languageEnglish
Pages (from-to)595-600
Number of pages6
JournalJournal of Antibiotics
Issue number5
Publication statusPublished - 2017 May 1

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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