Recent Developments in 14–3–3 Stabilizers for Regulating Protein–Protein Interactions: An Update

Abstract

14–3–3 proteins play a crucial role in the regulation of protein–protein interactions, impacting various cellular processes and disease mechanisms. Recent advancements have led to the development of stabilizers that enhance the binding of 14–3–3 proteins to clients, presenting promising therapeutic potentials. This perspective provides an updated overview of the latest developments in the field of 14–3–3 stabilizers, with a focus on their design, synthesis, and biological evaluation. We discuss the structural basis for the interaction between 14–3–3 proteins and their ligands, highlighting key modifications that enhance binding affinity and selectivity. Additionally, we explore the therapeutic applications of 14–3–3 stabilizers across major therapeutic areas such as cancer, metabolic disorders, and neurodegenerative diseases. By summarizing recent research findings and technological advancements, this perspective aims to shed light on the current state of 14–3–3 stabilizer developments and outline future directions for optimizing these compounds as effective therapeutic agents.