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

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Lack NA, Axerio-Cilies P, Tavassoli P, Han FQ, Chan KH, Feau C, LeBlanc E, Guns ET, Guy RK, Rennie PS, Cherkasov A

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. Epub 2011 Nov 18.

PubMed ID

22047606 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Flufenamic acid	Androgen receptor	IC 50 (nM)	>50000	N/A	N/A	Details