A 'rule of 0.5' for the metabolite-likeness of approved pharmaceutical drugs

Stephen O'Hagan, Neil Swainston, Julia Handl, Douglas B. Kell

Research output: Contribution to journalArticlepeer-review

Abstract

We exploit the recent availability of a community reconstruction of the human metabolic network (‘Recon2’) to study how close in structural terms are marketed drugs to the nearest known metabolite(s) that Recon2 contains. While other encodings using different kinds of chemical fingerprints give greater differences, we find using the 166 Public MDL Molecular Access (MACCS) keys that 90 % of marketed drugs have a Tanimoto similarity of more than 0.5 to the (structurally) ‘nearest’ human metabolite. This suggests a ‘rule of 0.5’ mnemonic for assessing the metabolite-like properties that characterise successful, marketed drugs. Multiobjective clustering leads to a similar conclusion, while artificial (synthetic) structures are seen to be less human-metabolite-like. This ‘rule of 0.5’ may have considerable predictive value in chemical biology and drug discovery, and may represent a powerful filter for decision making processes.
Original languageEnglish
Pages (from-to)323-339
Number of pages17
JournalMetabolomics
Volume11
Issue number2
Early online date19 Sep 2014
DOIs
Publication statusPublished - Apr 2015

Keywords

  • Cheminformatics
  • Drug-likeness
  • Genome-wide metabolic reconstruction
  • KNIME
  • Metabolite-likeness
  • Recon 2

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology

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