Methoxychalcone inhibitors of androgen receptor translocation and function

作者：Kim Yeong Sang; Kumar Vineet; Lee Sunmin; Iwai Aki; Neckers Len; Malhotra Sanjay V^*; Trepel Jane B

来源：Bioorganic & Medicinal Chemistry Letters, 2012, 22(5): 2105-2109.

DOI：10.1016/j.bmcl.2011.12.141

• Chalcone
• Antiandrogen
• Androgen receptor translocation
• Prostate cancer
• Hsp90

Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non-responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity. Published by Elsevier Ltd.

• 出版日期2012-3-1