In silico discovery of androgen receptor antagonists with activity in castration resistant prostate cancer.

ABSTRACT: Previously available androgen receptor (AR) antagonists (bicalutamide, flutamide, and nilutamide) have limited activity against AR in prostate cancers that relapse after castration [castration resistant prostate cancer (CRPC)]. However, recent AR competitive antagonists such as MDV3100, generated through chemical modifications to the current AR ligands, appear to have increased activity in CRPC and have novel mechanisms of action. Using pharmacophore models and a refined homology model of the antagonist-liganded AR ligand binding domain, we carried out in silico screens of small molecule libraries and report here on the identification of a series of structurally distinct nonsteroidal small molecule competitive AR antagonists. Despite their unique chemical architectures, compounds represent

SUBMITTER: Shen HC 

PROVIDER: S-EPMC3487628 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature