Drug-target network

Muhammed A. Yildirim, Kwang Il Goh, Michael E. Cusick, Albert László Barabási, Marc Vidal

Research output: Contribution to journalArticlepeer-review

1449 Citations (Scopus)

Abstract

The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein-protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration-approved drugs and proteins linked by drug-target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local clustering of drugs of similar types according to Anatomical Therapeutic Chemical classification. Topological analyses of this network quantitatively showed an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins. By including drugs currently under investigation, we identified a trend toward more functionally diverse targets improving polypharmacology. To analyze the relationships between drug targets and disease-gene products, we measured the shortest distance between both sets of proteins in current models of the human interactome network. Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed.

Original languageEnglish
Pages (from-to)1119-1126
Number of pages8
JournalNature Biotechnology
Volume25
Issue number10
DOIs
Publication statusPublished - 2007 Oct

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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