Antarlides: A New Type of Androgen Receptor (AR) Antagonist that Overcomes Resistance to AR‐Targeted Therapy. (25th January 2016)

• Record Type: Journal Article
• Authors: Saito, Shun; Fujimaki, Takahiro; Panbangred, Watanalai; Igarashi, Yasuhiro; Imoto, Masaya
• Is Part Of: Angewandte Chemie. Volume 128:Number 8(2016)
• Page Start: 2778
• Page End: 2782
• Publication Date: 2016-01-25
• Subjects: Androgenrezeptorantagonisten -- Krebs -- Naturstoffe -- NMR-Spektroskopie -- Wirkstoffresistenzen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201510079
• Languages: English
• ISSNs: 0044-8249

Abstract

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 of1 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.