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Chemokine receptor antagonists: overcoming developmental hurdles

Nature Reviews Drug Discovery volume 8, pages 23–33 (2009)Cite this article

Abstract

Chemokine receptors have a key role in the pathogenesis of autoimmune diseases, inflammation and viral infection. However, with the exception of selective CCR5 antagonists for HIV, the promise of obtaining new therapeutics related to chemokine receptors has not yet been realized. This article highlights some of the recent failures in the clinical trials of chemokine receptor antagonists and explores possible reasons as to why this might have occurred. Such reasons include the lack of predictability of animal models and redundancy of the target. A potential solution could be to develop drugs that target more than one receptor — known as polypharmacology — which could be a novel way to generate effective therapeutics.

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Figure 1: Structures of some chemokine receptor antagonists.
Figure 2: The design of dual angiotensin II (AT1) and endothelin (ETA) receptor antagonists.
Figure 3: Structures of non-peptide dual-chemokine receptor inhibitors.

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Acknowledgements

I would like to thank the reviewers for improving the clarity of this article. Any factual errors remaining are mine.

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  1. Richard Horuk is an adjunct professor at Touro University, 1310 Johnson Lane, Vallejo, California 94592, USA. Horuk@Pacbell.net,

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DATABASES

IUPHAR Receptor database

CCR1

CCR2

CCR3

CCR4

CCR5

CCR8

CCR9

CCR10

CXCR2

CXCR3

CXCR4

CX3CR1

FURTHER INFORMATION

ClinicalTrials.gov identifier NCT00542022

ClinicalTrials.gov identifier NCT00239655

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Horuk, R. Chemokine receptor antagonists: overcoming developmental hurdles. Nat Rev Drug Discov 8, 23–33 (2009). https://doi.org/10.1038/nrd2734

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