Pharmacometabolomics in Drug Discovery & Development: Applications and Challenges

Abstract

Volume 2 • Issue 5 • 1000e122 prevention, early detection, and monitoring the progression of diseases [13,14]. With high throughput/high resolution mass spectrometry and NMR techniques as well as various statistical models, many biomarkers in human disease were successfully identified to differentiate patients and health control groups, or to predict death [15]. It is very critical for the pharmaceutical industry to find biomarkers for disease and to indicate how people respond to a drug. Biomarkers can be used in predicting therapy response and as surrogate end points for clinical trials [16]. In one study, five metabolites were detected differently between the non-invasive tumors and the invasive tumors in gastric cancer patients, suggesting the selected tissue metabolites could probably be applied for clinical diagnosis of gastric cancer [17]. Many other applications of metabolomics in biomarker discovery have been succinctly summarized in several reviews [18,19]. Drug Target Identification & Validation Since the biochemical bases of many diseases come from the activity of particular enzymes, the pharmacometabolomics profile not only diagnose disease, but also reveal new drug targets and explore new treatment strategies. The alterations of cellular metabolic stages describe combination changes of genome, transcriptome and proteome. Therefore, pharmacometabolomics is a complementary tool for drug target identification and validation. In a serum metabolomic analysis, Chen et al. identified stearoyl-CoA desaturase 1 (SCD1) and its related lipid species which may serve as potential targets for treatment of inflammatory diseases [20]. 37 genetically determined metabolite traits were reported with strong association for various diseases [21]. The identification of associated metabolic traits may generate many new hypotheses for biomedical and pharmaceutical research. Among these genes, SLC16A9 (MCT9) was demonstrated as a carnitine efflux transporter responsible for carnitine efflux from absorptive epithelia into the blood [21]. Wei conducted a target-based metabolomics study to characterize metabolic response of Huh7.5 cells to genomic perturbation of HIF-1. The results identify a new therapeutic target by confirming HIF-1's regulatory role in tumor energy metabolism [22].