Inhibition of prostate cancer cell growth by second-site androgen receptor antagonists.

ABSTRACT: The impact of ligand binding on nuclear receptor (NR) structure and the ability of target cells to distinguish between different receptor-ligand complexes are key determinants of the pharmacological activity of NR ligands. However, until relatively recently, these mechanistic insights have not been used in a prospective manner to develop screens for NR modulators with specific therapeutic activities. Driven by the need for unique androgen receptor (AR) antagonists that retain activity in hormone-refractory prostate cancer, we developed and applied a conformation-based screen to identify AR antagonists that were mechanistically distinct from existing drugs of this class. Two molecules were identified by using this approach, D36 and D80, which interact with AR in a unique manner and alloster

SUBMITTER: Joseph JD 

PROVIDER: S-EPMC2715477 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature