molecular glue
A molecular glue is a small molecule that does not block a protein but instead sticks two proteins together that would not normally meet. Imagine a tiny dab of adhesive that fits in the gap between two surfaces, making them clasp hands; the glue's job is to create or strengthen a contact rather than to occupy an active site.
By forcing a new protein-protein interaction, a molecular glue can rewire what a protein does. The most celebrated use is in targeted protein degradation: a glue can pull a disease-causing protein up against the cell's disposal machinery, marking it for destruction. Other glues stabilize useful complexes or trap a protein in an inactive shape.
What makes molecular glues special is that they are usually small, drug-like, and able to act on protein surfaces long considered 'undruggable' because they are flat and lack a deep pocket. The challenge is that suitable glues are often discovered serendipitously, and rationally designing one to glue any chosen pair of proteins is still very hard.
Lenalidomide acts as a molecular glue, reshaping a ubiquitin-ligase surface so it grips a transcription factor and tags it for destruction.
A small molecule that induces a new contact between two proteins.
The thalidomide-derived drugs (lenalidomide and relatives) were later understood to act as molecular glues that recruit proteins for degradation.