The human androgen receptor (AR) is a proven therapeutic target in prostate cancer.
All current antiandrogens, such as Bicalutamide, Flutamide, Nilutamide, and Enzalutamide, target the buried hydrophobic androgen binding pocket of this protein. However, effective resistance mechanisms against these therapeutics exist such as mutations occurring at the target site. To overcome these limitations, the surface pocket of the AR called binding function 3 (BF3) was characterized as an alternative target for small molecule therapeutics. A number of AR inhibitors directly targeting the BF3 were previously identified by us ( J. Med. Chem. 2011 . 54 , 8563 ). In the current study, based on the prior results, we have developed structure-activity relationships that allowed designing a series of 2-((2-phenoxyethyl)thio)-1H-benzimidazole and 2-((2-phenoxyethyl)thio)-1H-indole as lead BF3 inhibitors. Some of the developed BF3 ligands demonstrated significant antiandrogen potency against LNCaP and Enzalutamide-resistant prostate cancer cell lines.
Written by:
Munuganti RS, Leblanc E, Axerio-Cilies P, Labriere C, Frewin K, Singh K, Hassona MD, Lack NA, Li H, Ban F, Tomlinson Guns E, Young R, Rennie PS, Cherkasov A. Are you the author?
Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada.
Reference: J Med Chem. 2013 Feb 14;56(3):1136-48
doi: 10.1021/jm3015712
PubMed Abstract
PMID: 23301637
