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A comprehensive map of molecular drug targets

Nature Reviews Drug Discovery volume 16, pages 1934 (2017) | Download Citation


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.

Key points

  • The definition of a drug target is crucial to the success of mechanism-based drug discovery. It is also increasingly important for efforts 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.

  • In this article, we synthesized and built on our previous approaches and systematically recompiled and comprehensively annotated the current list of drugs approved by the US FDA. We assigned to each drug their respective efficacy target or target set from the prescribing information and/or the scientific literature.

  • We curated a total of 893 human and pathogen-derived biomolecules through which 1,578 FDA-approved drugs act. These include 667 human-genome-derived proteins targeted by drugs for human disease.

  • We emphasize that even with a well-defined concept of efficacy there are challenges in making a clean unambiguous assignment in many cases, especially regarding how to treat protein complexes or drugs that bind to a number of closely related gene products.

  • We also mapped each drug (and thereby target) to the WHO Anatomical Therapeutic Chemical Classification System code as a way of obtaining a standard therapeutic indication for them.

  • With this mapping, we explored the footprint of target classes across disease areas, investigated the success of privileged target families and compiled a list of drug target orthologues for standard model organisms to develop a foundation for the deeper understanding of species differences, cross-species drug repositioning and applicability of animal models.

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The work of the authors is supported by the following institutes, organizations and grants: (1) Wellcome Trust Strategic Awards WT086151/Z/08/Z, WT104104/Z/14/Z to J.P.O., A.G., A.H. and A.P.B.; (2) the member states of EMBL to R.S., R.S.D, A.G., A.H., A.P.B.); (3) US National Institutes of Health (NIH) grants 1U54CA189205-01 to O.U., A.G., A.H., A.K., C.G.B., T.I.O. and J.P.O., and NIH grants P30CA118100 and UL1TR001449 to T.I.O.; and (4) B.A.-L. is funded by the Institute of Cancer Research. canSAR is funded by The Cancer Research UK grant to the Cancer Research UK Cancer Therapeutics Unit (grant C309/A11566). The authors thank many of their collaborators for discussions and valuable input in the preparation of this manuscript, in particular the members of the Illuminating the Druggable Genome consortium.

Author information

Author notes

    • Rita Santos

    Present address: Computational Biology and Target Sciences, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, UK.

    • Anneli Karlsson
    •  & John P. Overington

    Present address: BenevolentAI, 40 Churchway, London NW1 1LW, UK.


  1. European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

    • Rita Santos
    • , Anna Gaulton
    • , A. Patrícia Bento
    • , Ramesh S. Donadi
    • , Anneli Karlsson
    • , Anne Hersey
    •  & John P. Overington
  2. Translational Informatics Division, University of New Mexico School of Medicine, MSC09 5025, 700 Camino de Salud NE, Albuquerque, New Mexico 87131, USA.

    • Oleg Ursu
    • , Cristian G. Bologa
    •  & Tudor I. Oprea
  3. Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, UK.

    • Bissan Al-Lazikani


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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Bissan Al-Lazikani or Anne Hersey or Tudor I. Oprea or John P. Overington.

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    Deconvoluting the average number of drugs per target, and targets per drug.

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