Inhibitors for Androgen Receptor Activation Surfaces

摘要

Our research demonstrated a new protein interaction site on the androgen receptor. We showed that the site called BF3 has the characteristics of functioning in repression and likely binds one or more proteins. We are presently performing experiments to identify these proteins. We used X-ray crystallography to learn the binding mode of small molecule compounds that bind to this site. The BF3 site is allosteric because binding is accompanied by weakening the interaction of the androgen receptor with coactivators. X-ray crystallography demonstrated disorder of coactivator peptides that were well ordered before adding the compounds. Our studies suggest that compounds may be designed to target this site and weaken activity of the androgen receptor. Such compounds could form a new class of chemical therapeutics for treatment of prostate cancer.