Inducing or enhancing protein-protein interaction to develop drugs: Molecular glues with various biological activity

Over the past two decades, molecular glues (MGs) have gradually attracted the attention of the pharmaceutical community with the advent of MG degraders such as IMiDs and indisulam. Such molecules degrade the target protein by promoting the interaction between the target protein and E3 ligase. In addition, as a chemical inducer, MGs promote the dimerization of homologous proteins and heterologous proteins to form ternary complexes, which have great prospects in regulating biological activities. This review focuses on the application of MGs in the field of drug development including protein-protein interaction (PPI) stability and protein degradation. We thoroughly analyze the structure of various MGs and the interactions between MGs and various biologically active molecules, thus providing new perspectives for the development of PPI stabilizers and new degraders. [Display omitted] •Protein-protein interaction (PPI) is the primary means of regulating biological information. Molecular glue (MG) exhibit various biological activity through Inducing or enhancing protein-protein interaction.•PPI stabilizers up-regulate/down-regulate the physiological activity of key proteins to prevent the development of disease via stabilizing certain PPIs.•MG degraders stabilize PPIs between substrate protein and E3 ligase to form ternary complexes to lead the UPS-mediated degradation of substrate proteins.•Rational discovery technologies, such as chemical genetics, multicovalent chemoproteomic profiling, systemic data mining and transposable chemical handle strategy, have been developed to identify new MGs.