Chemical proteomics identifies unanticipated targets of clinical kinase inhibitors.

Kinases represent one of the most important target classes of current drug discovery efforts. However, because the vast majority of potential small-molecule therapeutics is directed toward the highly conserved ATP-binding cleft, kinase inhibitors often exhibit significant unintended off-target effects. A recent report describes a chemical proteomics methodology that enables the simultaneous in vivo quantification of the on- and off-binding targets of kinase inhibitors across hundreds of nucleotide-dependent enzymes.