Applied metabolomics in drug discovery

ABSTRACT

Introduction: The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs.

Areas covered: This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks.

Expert opinion: Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

KEYWORDS:

• Metabolomics
• metabonomics
• metabolic profiling
• drug discovery
• natural products
• chemical libraries
• metabolic network

Article highlights

• Metabolomics can enhance discovery and testing of new drugs, provide insight into the on- and off-target effects of drugs and provide valuable markers for clinical trials and applications.

• Combining experimental and computational metabolomics with high throughput drug testing as well as drug discovery can provide new compounds and drug leads for better, less toxic drugs.

• Experimental and analytical tools for metabolomics are developing fast and providing more sensitive methodologies and better methods for assignment and new molecule discovery.

• Natural product discovery and metabolomics are highly related as both attempt to extract molecular information from complex metabolic mixtures thus metabolomics methods directly apply to natural product discovery.

• Metabolomics can add molecular data to high-throughput screening methods of drugs.

This box summarizes key points contained in the article.

Declaration of interest

The authors are funded by the Government of Canada as part of a National Research Council Project. AS Culf is a Research Scientist Sussex Research Laboratories Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.