Figure 1.

Schematic properties of PPI inhibitors. (A) Small molecules or peptides can inhibit PPIs by binding to the interface (orthosteric) or a distal site (allosteric). Peptides are often derived from natural protein partners and can be either structured (e.g. helical) or disordered (e.g. random coil). (B) Categorization of PPIs based on buried surface area (BSA) and the affinity of the PPI creates four types of interactions. In the last 20+ years of PPI inhibitor discovery, the majority of reported inhibitors have been directed at the concise/strong qudrant (bottom left). These compounds also tend to have the best potency values.See the text for references.