title: A comprehensive map of molecular drug targets.
abstract: The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development. Here, we present an updated comprehensive map of molecular targets of approved drugs. We curate a total of 893 human and pathogen-derived biomolecules through which 1,578 US FDA-approved drugs act. These biomolecules include 667 human-genome-derived proteins targeted by drugs for human disease. Analysis of these drug targets indicates the continued dominance of privileged target families across disease areas, but also the growth of novel first-in-class mechanisms, particularly in oncology. We explore the relationships between bioactivity class and clinical success, as well as the presence of orthologues between human and animal models and between pathogen and human genomes. Through the collaboration of three independent teams, we highlight some of the ongoing challenges in accurately defining the targets of molecular therapeutics and present conventions for deconvoluting the complexities of molecular pharmacology and drug efficacy.
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.|Computational Biology and Target Sciences, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Santos
authors.affiliation: Translational Informatics Division, University of New Mexico School of Medicine, MSC09 5025, 700 Camino de Salud NE, Albuquerque, New Mexico 87131, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Ursu
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Gaulton
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: A Patrícia
authors.initials: AP
authors.lastname: Bento
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Ramesh S
authors.initials: RS
authors.lastname: Donadi
authors.affiliation: Translational Informatics Division, University of New Mexico School of Medicine, MSC09 5025, 700 Camino de Salud NE, Albuquerque, New Mexico 87131, USA.
authors.forename: Cristian G
authors.initials: CG
authors.lastname: Bologa
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.|BenevolentAI, 40 Churchway, London NW1 1LW, UK.
authors.forename: Anneli
authors.initials: A
authors.lastname: Karlsson
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Bissan
authors.initials: B
authors.lastname: Al-Lazikani
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Hersey
authors.affiliation: Translational Informatics Division, University of New Mexico School of Medicine, MSC09 5025, 700 Camino de Salud NE, Albuquerque, New Mexico 87131, USA.
authors.forename: Tudor I
authors.initials: TI
authors.lastname: Oprea
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.|BenevolentAI, 40 Churchway, London NW1 1LW, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Overington
mesh_terms: D062313:Databases, Pharmaceutical; D017277:Drug Approval; D016503:Drug Delivery Systems / Q000639:trends*; D055808:Drug Discovery / Q000639:trends*; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D010597:Pharmacogenetics / Q000639:trends*; D014481:United States; D014486:United States Food and Drug Administration