There is considerable evidence to suggest that progression of prostate cancers to castration- resistant is due to inappropriate activation of the androgen receptor (AR) and hence, the AR is a good target for the treatment of this disease. In this study we used two approaches to investigate AR activation and inhibition. We developed high-throughput, non-invasive, cell- based screening assays to rapidly and biologically assess factors that modulate prostate cancer growth and affect AR activity. Using these assays, we found that differentiated osteoblast-like condition media enhanced prostate cancer cell growth, but not AR activity. In addition, we applied this system to screen compounds, selected through in silico approaches against a crucial pocket on the AR protein. The application of our in silico tools and our cell based screening assay resulted in identification of 17 compounds out of 4 millions that can inhibit AR activity. Importantly, some of these compounds are...

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