Chemoproteomics: Towards Global Drug Target Profiling

Illuminating drugs’ mechanisms of action and their effects on the biomolecules of pathogens and humans is a much‐needed next step to facilitate pharmaceutical development. Although studies have linked some drugs to their therapeutic targets by using transcriptomics and genomics, these approaches have intrinsic limitations and cannot directly assess drugs’ effects on their protein targets. In this regard, chemoproteomic methods can detect protein–ligand interactions and quantitate the chemical or thermal stability changes of the entire detectible proteomes induced by drugs of interest. These widely applicable techniques have recently been adapted to deconvolute the mechanisms of action of antiparasitic drugs and successfully identified an essential target that was previously not known to be druggable. A continued effort to Integrate chemoproteomics into the drug‐development pipeline could greatly improve our understanding of drugs’ mechanisms, toxicity and pharmacodynamic properties.