Allosteric inhibitors of chemoattractant receptors: opportunities and pitfalls

Trends Pharmacol Sci. 2008 Jun;29(6):280-6. doi: 10.1016/ Epub 2008 Apr 20.


Given the central role of chemokines in infection, inflammation and immunity, chemokine receptors are a prime target for pharmacological intervention, and more so after the recent approval of chemokine receptor inhibitors for HIV. Allosteric inhibitors offer a largely unexploited opportunity to interfere with and modulate chemokine receptor activation and signaling. In addition to characterizing binding mode as a first step to understanding the specific mechanism underlying drug action, allosteric inhibitors pose new questions concerning different phases in drug discovery and pharmacological characterization, including the identification of appropriate screening tests, the evaluation of inhibitory effects on different signaling pathways and the implications of agonist- and signaling pathway-dependent inhibition for overall in vivo efficacy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation
  • Animals
  • Binding Sites
  • Chemokines / drug effects*
  • Chemokines / metabolism
  • Drug Delivery Systems*
  • Drug Design
  • Humans
  • Protein Binding
  • Receptors, Chemokine / antagonists & inhibitors*
  • Signal Transduction / drug effects


  • Chemokines
  • Receptors, Chemokine