September 22-23, 2015, New York, NY. Third Annual CHI Discovery on Target – Targeting the Ubiquitin Proteasome System: Exploring the Therapeutic Potential of Ubiquitin Ligases and Deubiquitinases (DUBs). Although the ubiquitin pathway remains a highly attractive source of new medicines for a variety of diseases, progress to the clinic for all ubiquitin-based experimental therapies except proteasome inhibitors has been slow.  Dr. Tauseef Butt, CEO of Progenra, described the company’s recent progress in developing selective inhibitors of ubiquitin pathway enzymes (E3 ligases, which conjugate ubiquitin to target proteins, and deubiquitylases, which de-conjugate ubiquitin). Focusing on USP7, an oncogenic protein that sustains tumor growth by a variety of molecular mechanisms, Dr. Butt described studies showing that Progenra’s novel inhibitors of this enzyme exert direct antitumor activity in a number of p53-positive and p53-negative animal models and, equally important, block cancer growth in immunocompetent mice by impairing the host animals’ regulatory T cell functions, thereby allowing effector T cells to eradicate implanted tumors. He presented evidence laying out the molecular mechanisms of these inhibitors in various cellular and in vivo settings. Progenra is developing these USP7 inhibitors as single agents or for combination treatments with established cancer immunotherapies to achieve durable clinical responses.