Molecular Glue”
A molecular glue is a small molecule that stabilizes the interaction between two proteins that do not normally interact. The most common type of molecular glue induces a novel interaction between a substrate receptor of an E3 ubiquitin ligase and a target protein leading to proteolysis of the target. Examples of molecular glues that induce degradation of protein targets include the immunomodulatory imide drug, which generate a novel interaction between a substrate and cereblon, a substrate receptor for Cullin-RING ubiquitin ligase 4. They work in a similar manner to PROTAC molecules, bringing about targeted protein degradation. Distinct from PROTAC molecules, molecular glues insert into a naturally occurring PPI interface, with contacts optimized for both the substrate and ligase within the same small molecule entity.