Format

Send to

Choose Destination
Drug Discov Today. 2014 Feb;19(2):171-82. doi: 10.1016/j.drudis.2013.07.014. Epub 2013 Jul 26.

Metabolomics and systems pharmacology: why and how to model the human metabolic network for drug discovery.

Author information

1
School of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK. Electronic address: dbk@manchester.ac.uk.
2
School of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.

Erratum in

  • Drug Discov Today. 2014 Nov;19(11):1828.

Abstract

Metabolism represents the 'sharp end' of systems biology, because changes in metabolite concentrations are necessarily amplified relative to changes in the transcriptome, proteome and enzyme activities, which can be modulated by drugs. To understand such behaviour, we therefore need (and increasingly have) reliable consensus (community) models of the human metabolic network that include the important transporters. Small molecule 'drug' transporters are in fact metabolite transporters, because drugs bear structural similarities to metabolites known from the network reconstructions and from measurements of the metabolome. Recon2 represents the present state-of-the-art human metabolic network reconstruction; it can predict inter alia: (i) the effects of inborn errors of metabolism; (ii) which metabolites are exometabolites, and (iii) how metabolism varies between tissues and cellular compartments. However, even these qualitative network models are not yet complete. As our understanding improves so do we recognise more clearly the need for a systems (poly)pharmacology.

PMID:
23892182
PMCID:
PMC3989035
DOI:
10.1016/j.drudis.2013.07.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center