Discovery of novel androgen receptor antagonists: a hybrid approach of pharmacophore-based and docking-based virtual screening.

Androgen receptor (AR) is an attractive target for the treatment of prostate cancer. An integrated pharmacophore-based and docking-based virtual screening approach was applied to identify novel AR antagonists with a distinct scaffold. The candidate compounds were evaluated for their abilities to inhibit prostate cancer cell proliferation and AR target gene prostate-specific antigen gene expression as well as the binding affinity to AR. A potent lead compound, T3, was discovered with the ability to inhibit prostate-specific antigen expression, with a similar binding affinity to AR, and with antiproliferative effects on AR-positive prostate cancer cells similar to that of MDV3100.