Abstract
A major function of the chemokine system is to coordinate the recruitment of leukocytes to specific locations within the tissues. The involvement of chemokine receptors in a multitude of inflammatory diseases, coupled with their belonging to the highly “druggable” GPCR superfamily, makes them excellent candidates for the development of novel drugs by the pharmaceutical industry. Despite descriptions in the literature of many specific small molecule chemokine receptor antagonists, none have yet shown efficacy in the clinical inflammatory setting. In this article, we discuss the successes and failures of chemokine receptor antagonists in the clinic and review a subset of molecules that are documented as having activity at two or more chemokine receptors. It may be that a more permissive approach, targeting several chemokine receptors with a single molecule will provide the next generation of anti-inflammatory drugs.
Keywords: Chemokine receptors, chemokines, GPCRs, antagonism
Current Topics in Medicinal Chemistry
Title: Small Molecule Antagonists of Chemokine Receptors - is Promiscuity a Virtue?
Volume: 10 Issue: 13
Author(s): James E. Pease and Richard Horuk
Affiliation:
Keywords: Chemokine receptors, chemokines, GPCRs, antagonism
Abstract: A major function of the chemokine system is to coordinate the recruitment of leukocytes to specific locations within the tissues. The involvement of chemokine receptors in a multitude of inflammatory diseases, coupled with their belonging to the highly “druggable” GPCR superfamily, makes them excellent candidates for the development of novel drugs by the pharmaceutical industry. Despite descriptions in the literature of many specific small molecule chemokine receptor antagonists, none have yet shown efficacy in the clinical inflammatory setting. In this article, we discuss the successes and failures of chemokine receptor antagonists in the clinic and review a subset of molecules that are documented as having activity at two or more chemokine receptors. It may be that a more permissive approach, targeting several chemokine receptors with a single molecule will provide the next generation of anti-inflammatory drugs.
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Cite this article as:
E. Pease James and Horuk Richard, Small Molecule Antagonists of Chemokine Receptors - is Promiscuity a Virtue?, Current Topics in Medicinal Chemistry 2010; 10 (13) . https://dx.doi.org/10.2174/156802610791561228
DOI https://dx.doi.org/10.2174/156802610791561228 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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