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Beyond the Human Genome

Examples of Nuclear Receptor Analysis in Model Organisms and Potential for Drug Discovery

  • Genomics in Drug Development
  • Published:
American Journal of Pharmacogenomics

Abstract

The nuclear receptor (NR) superfamily is a large group of related, pharmacologically important receptors, comprising the targets for over 10% of commonly prescribed drugs. Cross-genome analysis of NR sequence, structure, and biological function, provides an important source of information on the function of human NRs and thus plays a role in NR drug discovery. For example, research on the pregnane X receptor (PXR; NR1I2), constitutive androstane receptor (CAR; NR1I3), hepatocyte nuclear factor 4 (HNF4; NR2A1), and farnesoid X receptor (FXR) illustrate how the study of nonhuman orthologs has provided new insights into NR biology and has increased our understanding of human NRs and orphan NR function. Understanding differences between humans and pharmacological model species may provide useful tools for the development of new NR-binding drugs.

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Acknowledgements

The writing of this article was funded by GlaxoSmithKline, Inc. The authors have no conflicts of interest with any of the material contained in this review.

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Authors and Affiliations

  1. Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina, 27709, USA

    Jodi M. Maglich, Tim M. Willson &  John T. Moore

  2. Cambria Biosciences, Bedford, Massachusetts, USA

    Ann E. Sluder &  John T. Moore

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  1. Jodi M. Maglich
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  2. Ann E. Sluder
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  3. Tim M. Willson
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  4. John T. Moore
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Correspondence to John T. Moore.

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Maglich, J.M., Sluder, A.E., Willson, T.M. et al. Beyond the Human Genome. Am J Pharmacogenomics 3, 345–353 (2003). https://doi.org/10.2165/00129785-200303050-00005

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