How many protein pairs can we chemically target?

In the past 25 years, drugs acting on multiple targets by design have accounted for around one-fifth of annual new approvals. Beyond primary targets, drugs also interact, usually unintentionally, with multiple secondary targets. Here, we present a list of 64,222 target pairs currently being chemically targeted, representing 5% of all co-expressed dual combinations of proteins with a known interacting drug or bioactive ligand. In addition, we identified 7,253 target pairs that are likely to be chemically targetable, involving one protein with neither a drug nor a bioactive ligand known at present, but co-expressed and phylogenetically related to a chemically targeted protein. This catalogue of protein pairs offers a wealth of opportunities for the systematic design of future dual-action drugs.