Abstract

Inhibition Of Protein-Protein Interactions, Reflections And Projections

Michelle Arkin, Director, University of California San Francisco

Protein-protein networks are critical regulators of health and disease, yet are widely considered “undruggable” or, at best, “challenging.” Thus, there is an opportunity to greatly expand the range of chemical tools and drugs if we can identify which protein-protein interactions (PPI) are most amenable to small-molecule interference and what small-molecule discovery approaches are most likely to yield potent and selective modulators. This presentation will reflect on the past dozen years of PPI inhibitor discovery, and will introduce some of our forays into challenging targets. We favor combining a variety of approaches, including fragment-based ligand discovery, computation, and screening. Our long-term goal is to understand the molecular recognition features that lead to binding to dynamic interfaces and to develop inhibitors of these challenging targets.