Revealing promiscuous drug-target interactions by chemical proteomics

Molecular understanding of the (poly-)pharmacological activities of a drug cannot be achieved without a global characterization of its interactions with cellular components. Mass spectrometry based chemical proteomics approaches have recently been demonstrated as powerful tools for characterization of drug-target interactions directly from cells and cell extracts. At the same time, undesired cross-reactivities with other proteins within or outside the target class can be identified. This information can aid in the prediction of side effects and contribute towards optimization of candidate drug molecules. In this review, we describe recent advances in chemical proteomics and outline potential applications in drug discovery. Teaser Chemical proteomics enables characterization of drug-target and off-target interactions from native proteomes.