Development of a New Class of Drugs To Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers
Technical Report,30 Sep 2015,29 Sep 2016
University of Minnesota Minneapolis United States
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Prostate cancer is the most frequently diagnosed male cancer and second leading cause of male cancer death. Management of patients with advanced-stage disease relies on inhibiting the androgen receptor AR with conventional endocrine targeting therapies, and more recently with second-generation endocrine targeting therapies designed to block AR activity that re-emerges during castration. However, despite a growing armamentarium of drugs targeting the androgenAR signaling axis, progression of castration-resistant prostate cancer CRPC remains a major clinical challenge that undermines survival and quality of life for prostate cancer patients. The proposed research is focused on the pre-clinical development of VPC14228, a drug-like small molecule that targets the ARDNA interaction. During the first year of this award, we have made progress in investigating the functional effects of VPC14228 on DNA interaction and transcriptional activation mechanisms for AR, developing a definitive experimental and structural characterization of the VPC14228 interaction with the AR DBD, and conducting pre-clinical evaluation of VPC14228.