From the metabolic profiling of drug response to drug mode of action

One major bottleneck in the discovery and development of novel drug candidates is the identification of mechanisms of drug action. Extracting molecular signatures of drug action using functional genomic approaches, such as transcriptomics or proteomics, has become an invaluable tool to resolve drug targets and downstream effects using comparative analysis and network-based approaches. The unprecedented sensitivity and throughput of recent metabolomics platforms make metabolic drug profiling an emerging and particularly promising screening approach to aid and guide drug discovery. While metabolite concentrations provide biochemical signatures for monitoring the physiological effects of drugs and investigate their efficacy, selectivity, and toxicity, the application of metabolomics to predict drug Modes of Action (MoA) is still largely underexplored. This review surveys recent studies demonstrating the applicability of metabolomics to aid the systematic prediction of drug MoAs, and discusses how the emergence of large-scale metabolomics data provides new opportunities for lead selection and development at early stages of drug discovery.