Transient protein-protein interface (PPI) (PPI)

Transient protein-protein interfaces (PPIs) are the dynamic and reversible contact surfaces between proteins that mediate essential cellular processes such as signal transduction, apoptosis, and metabolic control (Nature Reviews Drug Discovery, 2014). Unlike permanent protein complexes, these interfaces form and dissociate in response to specific physiological triggers, acting as critical regulatory switches within biological networks (PubMed, PMC4189478). In many disease states, including cancer and autoimmune disorders, these transient interactions are often dysregulated, leading to uncontrolled cell growth or impaired immune responses (Journal of Medicinal Chemistry, 2020). While historically viewed as "undruggable" due to their large and relatively flat surface areas, modern drug discovery has successfully identified "hot spots" within these interfaces that can be targeted by small molecules or biologics (Chemical Reviews, 2016). Therapeutic agents like Venetoclax, which inhibits the Bcl-2/Bax interface, and Sotorasib, which targets the KRAS G12C interface, demonstrate the clinical viability of this approach (FDA, 2021). However, targeting transient PPIs remains challenging due to the need for high-affinity binders that can compete with endogenous proteins while maintaining favorable pharmacokinetic properties (Nature Reviews Drug Discovery, 2014).

Other names

Transient PPIDynamic protein-protein interactionReversible protein interfaceNon-obligate protein-protein interaction

Inhibition of protein-protein interactions by binding to interface hot spots, thereby preventing the formation of functional signaling complexes or inducing allosteric changes that disrupt binding.