Recent approval of bortezomib for use in multiple myeloma has validated the ubiquitin-proteasome system (UPS) as a druggable target, increasing interest in developing small molecule therapeutics for the UPS. Ubiquitin-specific protease 2 (USP2) has attracted a large degree of attention from the scientific community as a potential anti-cancer target. It has been linked to the stabilization of many cancer-associated proteins such as cyclin D1, fatty acid synthase, and MDM2 as well as a number of circadian rhythm enzymes. Herein, we describe the identification of a novel USP2 inhibitor from a quantitative high throughput screen, synthesis of analogs with improved potency and ADME properties, and preliminary characterization of their biological activity. These compounds will prove valuable in validating downstream protein targets of USP2 and in understanding the role USP2 in various diseases.

Identification of ubiquitin-specific protease 2 (USP2) inhibitors that promote cell cycle arrest via cyclin D1 destabilization

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.