Small-molecule inhibitors of protein-protein interactions

Targeting protein-protein interactions (PPIs) for therapeutic development was once considered undruggable due to the large and flat interactive surfaces that lack cavities. Facilitated by the development of new concepts, such as hotspots, screening techniques, and computational tools, various small molecules modulating PPIs have been achieved with a number of them having progressed into different phases of clinical trials and a portion recently reaching the market. In this article, we discuss the critical role of PPIs associated with various human diseases and different approaches to the identification of small molecular inhibitors targeting PPIs. We also highlight recent advances in developing such modulators as novel therapeutics.