Clues to molecular glues

Molecular Glues, here defined as small molecules that interact with two protein surfaces to induce or enhance affinity of these two proteins to each other, have received substantial interest as new drug modalities that can unlock otherwise inaccessible pharmacology. The recent serendipitous identification of several new molecular glues suggests that this mode of action is more prevalent than previously thought. However, the identification of molecular glues from scratch and their subsequent optimization still represent a formidable challenge. Here we review the recently discovered molecular glues, general features and insights that can be derived from them as well as from naturally occurring molecular glues, and the implications for drug discovery directed towards molecular glues.