Metabolic Pathways as Targets for Drug Screening

In the drug development process, candidate compounds are first screened for desirable biological properties such as effects on gene expression, signal transduction, or enzyme activity. The genetic and metabolic pathways used in the readouts are known as targets of the drug screening process. Despite advances in molecular targeting, proteomics and metabolomics, drug screening with molecular or metabolic targets have not produced the results that meet the need of the pharmaceutical industry in the selection of small molecules leads/targets for clinical testing. The relative lack of success in applying the -omics in drug screening is partly due to the inability of the –omics to account for metabolic regulation, a property of the cellular metabolic network. More recently, tracer-based metabolomics has been developed as an experimental approach for the study of cellular metabolic networks. Interconversion of metabolites are measured in terms of “extreme pathways” of the metabolic network which can be used for drug screening purposes. In this paper, these approaches for drug screening targeting genetic pathways (transcriptomics), biochemical pathways (metabolomics and fluxomics) and ‘extreme pathways” (tracer-based metabolomics) are compared. The advantages and limitations of these approaches for metabolic research and drug screening are discussed.