Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration-Resistant Prostate Cancers
Abstract
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 androgen/AR 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 AR:DNA 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1004012
Entities
People
- Daniel Gewirth
- Paul Rennie
- Scott M Dehm
Organizations
- University of Minnesota