Antarlides: A New Type of Androgen Receptor (AR) Antagonist that Overcomes Resistance to AR-Targeted Therapy

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Prostate cancer is treated with androgen receptor (AR) antagonists but most patients experience disease progression after long-term treatment with these compounds. Therefore, new AR antagonists are required for patient follow-up treatment. In the course of screening for a new AR antagonist, we isolated the novel compounds antarlides A-E (1-5) from Streptomyces sp. BB47. Antarlides are mutually isomeric with respect to the double bond and have a 22-membered-ring macrocyclic structure. The full stereostructure of 1 was established by chemical modifications, including methanolysis, the Trost method, acetonide formation, and the PGME method. 1-5 inhibited the binding of androgen to ARs in vitro. In addition, 2 inhibited the transcriptional activity of not only wild-type AR but also mutant ARs, which are seen in patients with acquired resistance to clinically used AR antagonists. Therefore, antarlides are a potent new generation of AR antagonists that overcome resistance.

Original languageEnglish
Pages (from-to)2728-2732
Number of pages5
JournalAngewandte Chemie - International Edition
Volume55
Issue number8
DOIs
Publication statusPublished - 2016 Feb 18

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Keywords

  • androgen receptor antagonists
  • cancer
  • drug resistance
  • natural products
  • NMR spectroscopy

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

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