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Trends in the exploitation of novel drug targets

Nature Reviews Drug Discovery volume 10, pages 579–590 (2011)Cite this article

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Key Points

  • Currently marketed drugs mediate their effects via only a limited number of molecular targets. The recent trends in drug development were analysed by extensively matching drugs with drug targets and correlating these with drug approval dates.

  • We have identified 435 effect-mediating targets that were encoded by single positions on the human genome.

  • We have also observed a steady rate of introduction of new drugs. Furthermore, in our data set there has been no substantial decrease in the number of new drugs approved by the US Food and Drug Administration each year.

  • On average, approximately 18 new drugs that act on targets that are encoded by the human genome are approved for the US market every year. The majority of new drugs target previously exploited structures that are encoded by the human genome.

  • On average, approximately 4.3 novel target drugs (NTDs) — that is, new drugs that target a previously unexploited molecular target that is encoded by the human genome — are approved for the US market every year.

  • Our drug–target network analysis shows a connection between the majority of drugs that form a giant interconnected network that we have termed the 'giant component'. However, NTDs have a greater tendency to be disconnected from the giant component and form small isolated networks. These smaller networks are of particular interest as they not only represent novel drug targets but also often represent new molecular mechanisms for treatment.

Abstract

The discovery and exploitation of new drug targets is a key focus for both the pharmaceutical industry and academic biomedical research. To provide an insight into trends in the exploitation of new drug targets, we have analysed the drugs that were approved by the US Food and Drug Administration during the past three decades and examined the interactions of these drugs with therapeutic targets that are encoded by the human genome, using the DrugBank database and extensive manual curation. We have identified 435 effect-mediating drug targets in the human genome, which are modulated by 989 unique drugs, through 2,242 drug–target interactions. We also analyse trends in the introduction of drugs that modulate previously unexploited targets, and discuss the network pharmacology of the drugs in our data set.

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Figure 1: Data curation process.
Figure 2: Classification of the currently utilized drug targets that are encoded by the human genome.
Figure 3: Number of new drugs affecting targets that are encoded by the human genome, and drugs affecting previously unexploited targets, that were approved by the FDA from 1983–2010.
Figure 4: Drug–target network: summary.
Figure 5: Drug–target network: selected networks.
Figure 6: Isolated smaller networks of drugs with novel targets that were approved between 2005 and 2010, and their corresponding target-encoding genes.

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Acknowledgements

The authors would like to thank J. Weigelt, Karolinska Institute, Stockholm, for providing valuable comments on an early version of the manuscript. These studies were supported by the Swedish Research Council, the Novo Nordisk Foundation and the Swedish Brain Research Foundation.

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Authors and Affiliations

  1. Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala Biomedical Center, 75124, Uppsala, Sweden

    Mathias Rask-Andersen, Markus Sällman Almén & Helgi B. Schiöth

  2. Department of Neuroscience, Uppsala Biomedical Center, BOX 593, 75124, Uppsala, Sweden

    Helgi B. Schiöth

Authors
  1. Mathias Rask-Andersen
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  2. Markus Sällman Almén
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  3. Helgi B. Schiöth
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Corresponding author

Correspondence to Helgi B. Schiöth.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information S1 (table)

Drug target dataset (XLS 460 kb)

Supplementary information S2

List of all gene abbreviations included in Table 1 (PDF 239 kb)

Supplementary information S3

Drug-target network: summary (PDF 759 kb)

Related links

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FURTHER INFORMATION

Drugs@FDA website

DrugBank database website

Drugs.com website

FDA Orange book

IMS Health

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Rask-Andersen, M., Almén, M. & Schiöth, H. Trends in the exploitation of novel drug targets. Nat Rev Drug Discov 10, 579–590 (2011). https://doi.org/10.1038/nrd3478

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