'Metabolite-likeness' as a criterion in the design and selection of pharmaceutical drug libraries

Drug Discov Today. 2009 Jan;14(1-2):31-40. doi: 10.1016/j.drudis.2008.10.011. Epub 2008 Dec 26.


Present drug screening libraries are constrained by biophysical properties that predict desirable pharmacokinetics and structural descriptors of 'drug-likeness' or 'lead-likeness'. Recent surveys, however, indicate that to enter cells most drugs require solute carriers that normally transport the naturally occurring intermediary metabolites and many drugs are likely to interact similarly. The existence of increasingly comprehensive summaries of the human metabolome allows the assessment of the concept of 'metabolite-likeness'. We compare the similarity of known drugs and library compounds to naturally occurring metabolites (endogenites) using relevant cheminformatics molecular descriptor spaces in which known drugs are more akin to such endogenites than are most library compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Transport
  • Databases, Factual
  • Drug Design*
  • Humans
  • Metabolome
  • Pharmaceutical Preparations / chemistry*
  • Pharmaceutical Preparations / metabolism
  • Small Molecule Libraries*
  • Structure-Activity Relationship


  • Pharmaceutical Preparations
  • Small Molecule Libraries