Protein-protein interactions (PPIs) are very attractive targets for drug development as they play important roles in regulating many aspects of pathophysiologies. It has recently been revealed that the functionally important region of most PPIs is small enough to be modulated by small molecules. Thus, many studies in this field have achieved amazing progress, together with diverse and advanced screening technologies. Areas covered: This article presents screening technologies to identify small molecule inhibitors of PPIs in addition to discussing the suitability of PPIs as molecular targets. The phases in the processes of selecting compounds are discussed and appropriate steps are proposed, including methodologies to test binding affinity, kinetics, structural analysis, and cellular function. Expert opinion: Targeting PPIs is still a challenging approach in drug development and relatively few small molecules have reached clinical development. Potential candidates should be assessed and optimized by properly using the multiple assay systems to develop ideal small molecule drugs. Although there remain some barriers to be overcome, small molecule inhibitors of PPIs are fascinating and first-in-class as therapeutic agents to treat various diseases.
Keywords: High-throughput screening; hot spot; protein–protein interaction; small molecule.