The emerging field of chemo- and pharmacoproteomics.

The emerging field of chemo- and pharmacoproteomics studies the mechanisms of action of bioactive molecules in a systems pharmacology context. In contrast to traditional drug discovery, pharmacoproteomics integrates the mechanism of a drug's action, its side effects including toxicity, and the discovery of new drug targets in a single approach. Thus, it determines early favorable (e.g. multiple kinase target in cancer drugs) and unfavorable (e.g. side effects) polypharmacology. Target profiling is accomplished using either active site-labeling probes or immobilized drugs. This strategy identifies direct targets and has in fact enabled even the determination of binding curves and half maximum inhibitory concentrations of these targets. In addition, the enrichment greatly reduces the complexity of the proteome to be analyzed by quantitative MS. Complementary to these approaches, global proteomics profiling studying drug treatement-induced changes in protein expression levels and/or post-translational modification status have started to become possible mostly due to significant improvements in instrumentation. Particularly, when using multidimensional separations, a considerable proteome depth of up to 10 000 proteins can be achieved with current state-of-the-art mass spectrometers and bioinformatics tools. In summary, chemo- and pharmacoproteomics has already contributed significantly to the identification of novel drug targets and their mechanisms of action(s). Aided by further technological advancements, this interdisciplinary approach will likely be used more broadly in the future.