Metabolomics Creative Proteomics

Metabolomics and Drug Development

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Metabolomics

For the past 40 years, the standard drug development model has been to identify disease causative genes by means of GWAS or whole genome sequencing, purify target proteins and screen lead compounds at high throughput, and then test drug effects in animal models and ultimately in human trials. This current model is increasingly inefficient, time-consuming and expensive. Only a very small percentage of drugs make it to the investigational stage or through to Phase I clinical trials. Therefore, shortening the development cycle and fully evaluating the toxicity of drug candidates are issues to be addressed in drug development.

Metabolomics reflects the series of biological events of pathophysiological processes by revealing the trajectory of overall changes in metabolism under the influence of intrinsic and extrinsic factors. It can perform dynamic qualitative and quantitative analysis of small molecule metabolites in organisms, find out the relative relationship between changes in metabolites and physiological and biochemical changes in organisms, identify drug metabolites and metabolic changes in organisms induced by drug action, and thus obtain information about drug metabolic effects and pharmacological and toxicological aspects.

In the field of new drug discovery and development, drug target discovery is important, and new bioactive substances are usually discovered through high-throughput screening methods. However, the effects of new drugs are ultimately confirmed in whole animal pharmacology and disease models before biologically active compounds can be transformed into candidates for development studies. Metabolomics, as a systematic approach, can play a huge role in these efforts. Metabolomic studies can differentiate the metabolic states of different animal models, search for metabolic differences in human disease states, and find animal models more suitable for studying human diseases.

A summary of applications of metabolomics in four stages of drug discovery and developmentFig 1. A summary of applications of metabolomics in four stages of drug discovery and development (Lu et al., 2017).

Metabolomics Technology

Metabolomics consists of untargeted metabolomics and targeted metabolomics. As an unbiased metabolomic analysis, untargeted metabolomics is easy to handle and can reflect the metabolomic characteristics of biological samples comprehensively and systematically, but it has a limited linear range, poor reproducibility, and complicated metabolite confirmation. Targeted metabolomics has a wide linear range, good reproducibility and sensitivity, and simple metabolite confirmation, but requires prior knowledge of the analyte, which is a kind of biased metabolomics analysis. The combination of the two can be a powerful tool for the discovery and accurate quantification of differential metabolites, and has a wide range of applications in disease research, confirmation of animal models of disease, drug development, drug screening, efficacy and toxicity evaluation, drug mechanism of action and clinical evaluation, plant metabolic function, and microbial metabolic function research.

Over the past 15 years, the following three techniques have evolved into major tools for metabolomics research: nuclear magnetic resonance (NMR) mapping, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These three research techniques cover the detection of many kinds of organic compounds, including lipids, amino acids, glycans, organic amines and organic acids.

Creative Proteomics is equipped with advanced instrumentation to provide you with high-quality metabolomics services. We combine ultra-high performance liquid chromatography (UHPLC) with ultra-high resolution instrumentation that provides sufficient resolution to distinguish metabolites from their chemical backgrounds, solving problems such as chemical noise and data redundancy, and obtaining more accurate data that helps to dig deeper into the information contained therein.

Reference

  1. Lu, Y., & Chen, C. (2017). Metabolomics: bridging chemistry and biology in drug discovery and development. Current Pharmacology Reports, 3(1), 16-25.
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