LC-MS/Proteomics: a platform for the identification and selection of drug targets
Conventional, hypothesis-driven biological research is conducted by studying the effect of a perturbation on a targeted cellular process. By using focused experimental analysis strategies, only a subset of the effects of such a perturbation can be explored, the large-scale implications having to be ignored. Proteomic technologies bring unsurpassed capabilities for generating a holistic view of the complex processes that control the growth and proliferation of a cell, and represent, therefore, a powerful approach for elucidating the molecular mechanisms of disease progression and response to therapeutic drugs. In this work, the potential of proteomic technologies, as completed on liquid chromatography (LC)-mass spectrometry detection (MS) platforms, for the discovery of networked drug-target clusters, as well as the implications for future drug discovery efforts, are discussed.
During the past two decades, the discovery of novel drugs and drug targets has become the lead objective of many academic, government, corporate and clinical laboratories. Drug development is a lengthy (8-15 years), costly (100 million to 5 billion USD per drug) and tedious process that consists of several major steps (1-3): (a) target identification and validation, (b) drug discovery through high-throughput screening of compound libraries and hit generation, (c) hit-to-lead, lead optimization and pre-clinical development, (d) clinical trials, and (e) FDA approval, launch and post-launch evaluations (Figure 1).The process is triggered by basic biomedical research, often occurring in academic laboratories, that results in the identification of a gene or gene product (mRNA or protein) with an essential biochemical and/or physiological role of relevance to a disease. Such molecular entities become drug targets after their presence, function and role are confirmed by validation assays.
The advent of “omic” technologies (genomics, transcriptomics, proteomics, metabolomics) has entertained hopes for a speedy and cost-effective discove ...