Targeting protein-protein interactions with low molecular weight and short peptide modulators: insights on disease pathways and starting points for drug discovery

Interfering specifically with large protein interfaces is still an open challenge. The initial concerns about the unfavorable physicochemical properties of many of these modulators are nowadays less acute with several molecules lying beyond the rule of 5, orally available and successful in clinical trials. As the cost of biologics interfering with PPIs is very high, it would seem reasonable to put more effort, both in academia and the private sectors, on actively developing novel low molecular weight compounds and short peptides to perform this task.