Drug target deconvolution by chemical proteomics

Drug target deconvolution is a process where the action of a drug, a small molecule, is characterised by identifying the proteins binding the drug and initiating the biological effect. The biological relevant target has to be extracted, or deconvoluted, from a list of proteins identified in such an approach. Beside the medically desired action of the drug, the identification of other proteins binding the drug can help to identify side effects and toxicity at a very early stage of drug development. The current approach to identify the proteins binding to the drug is an affinity-enrichment based approach, where the drug molecule is immobilised to a matrix through a linker and the proteins binding to the drug are identified by proteomics.

• Chemical proteomics allows unbiased identification of protein targets of drugs. • Potential off-targets explaining side effects and toxicity can be identified. • Chemical proteomics enables the understanding of the action of drugs. • The binding specificity of drugs in clinics was determined by competition experiments.