%A O'Hagan,Steve %A Kell,Douglas B. %D 2015 %J Frontiers in Pharmacology %C %F %G English %K drug transporters,Cheminformatics,endogenites,Metabolomics,Encodings %Q %R 10.3389/fphar.2015.00105 %W %L %M %P %7 %8 2015-May-13 %9 Original Research %+ Douglas B. Kell,School of Chemistry, The University of Manchester,Manchester, UK,dbk@manchester.ac.uk %+ Douglas B. Kell,The Manchester Institute of Biotechnology, The University of Manchester,Manchester, UK,dbk@manchester.ac.uk %# %! Drug-endogenite similarities and substructures %* %< %T Understanding the foundations of the structural similarities between marketed drugs and endogenous human metabolites %U https://www.frontiersin.org/articles/10.3389/fphar.2015.00105 %V 6 %0 JOURNAL ARTICLE %@ 1663-9812 %X Background: A recent comparison showed the extensive similarities between the structural properties of metabolites in the reconstructed human metabolic network (“endogenites”) and those of successful, marketed drugs (“drugs”).Results: Clustering indicated the related but differential population of chemical space by endogenites and drugs. Differences between the drug-endogenite similarities resulting from various encodings and judged by Tanimoto similarity could be related simply to the fraction of the bitstrings set to 1. By extracting drug/endogenite substructures, we develop a novel family of fingerprints, the Drug Endogenite Substructure (DES) encodings, based on the ranked frequency of the various substructures. These provide a natural assessment of drug-endogenite likeness, and may be used as descriptors with which to derive quantitative structure-activity relationships (QSARs).Conclusions: “Drug-endogenite likeness” seems to have utility, and leads to a simple, novel and interpretable substructure-based molecular encoding for cheminformatics.