Targeting the Binding Function 3 (Bf3) Site of the Human Androgen Receptor Through Virtual Screening.
Lack, N.A., Axerio-Cilies, P., Tavassoli, P., Han, F.Q., Chan, K.H., Feau, C., Leblanc, E., Guns, E.T., Guy, R.K., Rennie, P.S., Cherkasov, A.(2011) J Med Chem 54: 8563
- PubMed: 22047606 
- DOI: https://doi.org/10.1021/jm201098n
- Primary Citation of Related Structures:  
2YLO, 2YLP, 2YLQ, 3ZQT - PubMed Abstract: 
The androgen receptor (AR) is the best studied drug target for the treatment of prostate cancer. While there are a number of drugs that target the AR, they all work through the same mechanism of action and are prone to the development of drug resistance. There is a large unmet need for novel AR inhibitors which work through alternative mechanism(s). Recent studies have identified a novel site on the AR called binding function 3 (BF3) that is involved into AR transcriptional activity. In order to identify inhibitors that target the BF3 site, we have conducted a large-scale in silico screen followed by experimental evaluation. A number of compounds were identified that effectively inhibited the AR transcriptional activity with no obvious cytotoxicity. The mechanism of action of these compounds was validated by biochemical assays and X-ray crystallography. These findings lay a foundation for the development of alternative or supplementary therapies capable of combating prostate cancer even in its antiandrogen resistant forms.
Organizational Affiliation: 
Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada.