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Characterization of Novel Anti‐androgens as Potential Prostate Cancer Therapeutics

Anti‐androgens are the gold standard of care for treatment of advanced prostate cancer (PCa). The purpose of this study was to assess novel anti‐androgens PLM1, PLM6, and PAN52 designed and synthesized in the Koh laboratory. These compounds are based on the clinical standard bicalutamide, but have expanded aryl sulfonyl moieties. PLM6 and PAN52, but not PLM1, are thought to have unique mechanisms of action based on their ability to evade progression to anti‐androgen insensitivity in vitro. Prevention of androgen receptor (AR) nuclear translocation was found to correlate with evasion of anti‐androgen resistance in prostate cancer cell lines. Furthermore, these novel anti‐androgens were found to down‐regulate the androgen receptor, which may contribute to their efficacy. Statistically significant increases in prostatic apoptosis were observed in C57/Bl6 mice treated intraperitoneally with PLM6 and PAN52, indicating that these compounds hold promise as therapy for advanced prostate cancer. Motivated by these findings, we are exploring compounds with increased potency.