Androgen receptor-cofactor interactions as targets for new drug discovery.

Cofactor recruitment is a crucial regulatory step in nuclear receptor signal transduction. Given the obligate nature of interactions between cofactors and these receptors for transcriptional activity, it is likely that drugs that target coactivator interaction surfaces will function as pure antagonists with particular utility in the treatment of estrogen- and androgen-dependent cancers. Recent crystallographic analysis of one of the major protein-protein interaction surfaces on the androgen receptor has raised expectations that it will be possible to develop small-molecule antagonists that block cofactor interactions.