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A comprehensive map of molecular drug targets.

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Date
2017-01
ICR Author
Al-Lazikani, Bissan
Author
Santos, R
Ursu, O
Gaulton, A
Bento, AP
Donadi, RS
Bologa, CG
Karlsson, A
Al-Lazikani, B
Hersey, A
Oprea, TI
Overington, JP
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Type
Journal Article
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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.
URI
https://repository.icr.ac.uk/handle/internal/947
DOI
https://doi.org/10.1038/nrd.2016.230
Collections
  • Cancer Therapeutics
Subject
Humans
Drug Delivery Systems
Drug Approval
Pharmacogenetics
Genome, Human
United States Food and Drug Administration
United States
Drug Prescriptions
Genetic Variation
Drug Discovery
Databases, Pharmaceutical
Research team
Computational Biology and Chemogenomics
Language
eng
Date accepted
2016-12-02
License start date
2017-01
Citation
Nature reviews. Drug discovery, 2017, 16 (1), pp. 19 - 34

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