Abstract

Understanding the target and mode of action of compounds identified through phenotypic screening can greatly facilitate the process of drug discovery and development. Chemical proteomics can provide a powerful, unbiased route to the identification of the molecular targets of phenotypically active compounds. Unlike many of the other approaches used for drug target identification, chemical proteomics has the distinct advantage of providing evidence of on-target engagement, demonstrating physical interactions between compounds of interest and their molecular targets. The Wyllie lab employ a broad range of chemical proteomics strategies to identify the molecular targets of compounds showing promise for the treatment of malaria and several neglected tropical diseases, including standard chemical pulldown, µ-mapping and thermal proteome profiling. The pros and cons of each method will be discussed and examples of their practical use for target ID given.