Investigators have developed small molecule inhibitors that modulate AR nuclear localization and activation. Dr. Wang and colleagues have identified three novel small molecules that specifically inhibit nuclear localization of AR in vitro. These small molecules did not inhibit nuclear localization
of other ligand-dependent transcription factors such as glucocorticoid receptor or the estrogen receptor.

Background
Castration-resistant prostate cancer (CRPC) is
currently incurable and makes prostate cancer
the second most common cause of cancer death
among men in the United States. Multiple studies have shown that the androgen receptor (AR) is activated via multiple mechanisms including AR overexpression, mutation, and/or hypersensitization to residual androgens within the tumor cells in patients relapsed after androgen deprivation therapy.

The androgen receptor is an excellent therapeutic target for castration-resistant prostate cancer. AR is localized to the nuclei of castration-resistant prostate cancer cells under androgen-deprived conditions. Since AR is an androgen-dependent transcription factor, nuclear localization of AR in these castration-resistant prostate cancer cells is necessary for AR activation.
Identification and characterization of small
molecules capable of blocking AR nuclear localization in CRPC cells will have significant clinical relevance.

Stage of Development
1. Tumor xenograft data is available
2. PK and Tox studies are underway

Provisional Patent Application filed

File Number: 2501 

Disease: Cancer