Unravelling the mechanisms underpinning chemokine receptor activation and blockade by small molecules: A fine line between agonism and antagonism?

E. Wise*, J. E. Pease

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Chemokines are a family of small basic proteins which induce the directed migration of cells, notably leucocytes, by binding to specific GPCRs (G-protein-coupled receptors). Both chemokines and their receptors have been implicated in a host of clinically important diseases, leading to the notion that antagonism of the chemokine-chemokine receptor network may be therapeutically advantageous. Consequently, considerable effort has been put into the development of small-molecule antagonists of chemokine receptors and several such compounds have been described in the literature. One curious by-product of this activity has been the description of several small-molecule agonists of the receptors, which are typically discovered following the optimization of lead antagonists. In this review we discuss these findings and conclude that these small-molecule agonists might be exploited to further our understanding of the molecular mechanisms by which chemokine receptors are activated.

Original languageEnglish
Pages (from-to)755-759
Number of pages5
JournalBiochemical Society Transactions
Volume35
Issue number4
DOIs
Publication statusPublished - Aug 2007
Externally publishedYes

Keywords

  • Allosteric modulator
  • Antagonist
  • Chemokine receptor
  • G-protein-coupled receptor (GPCR)
  • Signalling

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