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Promiscuous drugs as therapeutics for chemokine receptors

Published online by Cambridge University Press:  06 January 2009

Richard Horuk
Affiliation:
Department of Pharmacy, Touro University, 1310 Johnson Lane, Vallejo, CA 94592, USA. Tel: +1 925 708 0358; E-mail: horuk@pacbell.net

Abstract

Chemokine receptor antagonists that held much promise for the treatment of autoimmune and inflammatory diseases have recently performed poorly in clinical trials, resulting in disappointment for both pharmaceutical companies and patients. This review focuses on the redundancy of the molecular target as one potential reason for the failure of some of these antagonists to fulfil their initial promise, and discusses the use of drugs that are capable of interacting with more than one drug target – so-called promiscuous drugs – as possible approaches to overcome this difficulty. Several clinically approved promiscuous drugs, such as aspirin and olanzapine, are already used successfully. This review discusses examples of promiscuous drugs for G-protein-coupled receptors, including progress in developing dual-specific chemokine receptor antagonists, and considers evidence for the possible therapeutic utility of such drugs.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

An excellent resource of databases and information on all things pertaining to G-protein-coupled receptors can be found at: http://www.gpcr.org/7tm/

A database of G-protein-coupled receptors maintained by the International Union of Pharmacology (IUPHAR) gives detailed information for all GPCRs, including useful information on their ligands, agonists, antagonists and selected publications: http://www.iuphar-db.org/GPCR/ReceptorFamiliesForward

The DrugBank database is an excellent resource providing chemical, pharmacological and pharmaceutical information for close to 4800 drugs of biological and clinical interest: http://www.drugbank.ca

Roth, B.L., Sheffler, D.J. and Kroeze, W.K. (2004) Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nature Reviews Drug Discovery 3, 353-359CrossRefGoogle ScholarPubMed
Morphy, R., Kay, C. and Rankovic, Z. (2004) From magic bullets to designed multiple ligands. Drug Discovery Today 9, 641-651CrossRefGoogle ScholarPubMed
Murphy, P.M. et al. (2000) International Union of Pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacological Reviews 52, 145-176Google ScholarPubMed
Roth, B.L., Sheffler, D.J. and Kroeze, W.K. (2004) Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nature Reviews Drug Discovery 3, 353-359CrossRefGoogle ScholarPubMed
Morphy, R., Kay, C. and Rankovic, Z. (2004) From magic bullets to designed multiple ligands. Drug Discovery Today 9, 641-651CrossRefGoogle ScholarPubMed
Murphy, P.M. et al. (2000) International Union of Pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacological Reviews 52, 145-176Google ScholarPubMed