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GPCRs: From Deorphanization to Lead Structure Identification pp 105–144Cite as

Orphan Seven Transmembrane Receptor Screening

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Part of the book series: Ernst Schering Foundation Symposium Proceedings ((SCHERING FOUND,volume 2006/2))

Abstract

Drug discovery has successfully exploited the superfamily of seven transmembrane receptors (7TMR), with over 35% of clinically marketed drugs targeting them. However, it is clear that there remains an undefined potential within this protein family for successful drugs of the future. The human genome sequencing project identified approximately 720 genes that belong to the 7TMR superfamily. Around half of these genes encode sensory receptors, while the other half are potential drug targets. Natural ligands have been identified for approximately 215 of these, leaving 155 receptors classified as orphan 7TMRs having no known ligand. Deorphanisation of these receptors by identification of natural ligands has been the traditional method enabling target validation by use of these ligands as tools to define biological relevance and disease association. Such ligands have been paired with their cognate receptor experimentally by screening of small molecule and peptide ligands, reverse pharmacology and the use of bioinformatics to predict candidate ligands. In this manuscript, we review the methodologies developed for the identification of ligands at orphan 7TMRs and exemplify these with case studies.

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  1. Screening and Compound Profiling, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK

    M. J. Wigglesworth, L. A. Wolfe III & A. Wise

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  1. M. J. Wigglesworth
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  2. L. A. Wolfe III
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  3. A. Wise
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Correspondence to M. J. Wigglesworth .

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H. Bourne R. Horuk J. Kuhnke H. Michel

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Wigglesworth, M.J., Wolfe, L.A., Wise, A. (2007). Orphan Seven Transmembrane Receptor Screening. In: Bourne, H., Horuk, R., Kuhnke, J., Michel, H. (eds) GPCRs: From Deorphanization to Lead Structure Identification. Ernst Schering Foundation Symposium Proceedings, vol 2006/2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/2789_2006_006

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