1. Academic Validation
  2. Targeting the binding function 3 (BF3) site of the human androgen receptor through virtual screening

Targeting the binding function 3 (BF3) site of the human androgen receptor through virtual screening

  • J Med Chem. 2011 Dec 22;54(24):8563-73. doi: 10.1021/jm201098n.
Nathan A Lack 1 Peter Axerio-Cilies Peyman Tavassoli Frank Q Han Ka Hong Chan Clementine Feau Eric LeBlanc Emma Tomlinson Guns R Kiplin Guy Paul S Rennie Artem Cherkasov
Affiliations

Affiliation

  • 1 Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada.
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.

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