Identification of small molecule inhibitors of DUB3

National Center For Advancing Translational Sciences

Investigators

Abstract

The goal of this project to identify compounds that can selectively inhibit DUB3 through a de novo chemical screen of compounds from NCATS collections. During this period, the research team have optimized and implemented a high-throughput biochemical assay and screened NCATS compound collections. The identified hits will be cherrypicked, validated and counterscreened for specificity against other closely-related DUBs. Additionally, hits will be validated in cellular assays for their effect on ER and AR levels. The resulting compound activity profiles will be reviewed, and a medicinal chemistry campaign will be initiated for the most promising chemotypes. Lead compounds will then be advanced for evaluation in relevant models/assays of hormone-resistant prostate and breast cancer.