title: 'Metabolite-likeness' as a criterion in the design and selection of pharmaceutical drug libraries.
abstract: 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.
authors.affiliation: School of Chemistry and The Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess St, Manchester M1 7DN, UK. paul.dobson@manchester.ac.uk
authors.forename: Paul D
authors.initials: PD
authors.lastname: Dobson
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Patel
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
mesh_terms: D001692:Biological Transport; D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D055442:Metabolome; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries