2--6--dimethoxychalcone and Prostatic-Neoplasms

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.

Topics: Androgen Antagonists; Cell Line, Tumor; Chalcones; Gene Expression Regulation, Neoplastic; HSP90 Heat-Shock Proteins; Humans; Male; Prostatic Neoplasms; Protein Transport; Receptors, Androgen