Small-molecule inhibitors of protein-protein interactions: progressing toward the reality.

ABSTRACT: The past 20 years have seen many advances in our understanding of protein-protein interactions (PPIs) and how to target them with small-molecule therapeutics. In 2004, we reviewed some early successes; since then, potent inhibitors have been developed for diverse protein complexes, and compounds are now in clinical trials for six targets. Surprisingly, many of these PPI clinical candidates have efficiency metrics typical of "lead-like" or "drug-like" molecules and are orally available. Successful discovery efforts have integrated multiple disciplines and make use of all the modern tools of target-based discovery-structure, computation, screening, and biomarkers. PPIs become progressively more challenging as the interfaces become more complex, i.e., as binding epitopes are displayed on prim

SUBMITTER: Arkin MR 

PROVIDER: S-EPMC4179228 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature