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We discuss how molecular glue discovery is shifting from serendipitous findings to a more rational strategy for drug discovery.

Our in the Journal of the American Chemical Society highlights how advances in chemical library design, proximity-induced pharmacology, genomic screening and artificial intelligence are helping researchers identify molecular glues. These are small molecules that stabilise protein–protein interactions, forcing two proteins into proximity to rewire cellular pathways. Historically, the best examples were found by accident and only later understood as proximity-inducing drugs. We see that the field is now shifting from serendipity to strategy, as described in this perspective.

The article also explores how molecular glues could be used beyond targeted protein degradation to rewire cellular pathways and selectively modulate protein function, opening new opportunities in chemical biology and medicine.

Congratulations to all authors on this perspective!