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Related Experiment Videos

Chemokines in allergy.

David Chantry1, Laurence E Burgess

  • 1Icos Corporation, 22021 20th Ave., Bothell, WA 98021, USA. lburgess@arraybiopharma.com

Current Drug Targets. Inflammation and Allergy
|October 17, 2003
PubMed
Summary

Targeting chemokine receptors CCR3, CCR4, and CCR8 offers a promising strategy for developing orally bioavailable small molecule inhibitors to treat allergic diseases by blocking inflammatory cell migration.

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Area of Science:

  • Immunology
  • Pharmacology
  • Molecular Biology

Background:

  • Allergic diseases like atopic dermatitis, asthma, and allergic rhinitis are significant healthcare burdens.
  • Understanding these conditions as dysregulated inflammatory responses has identified new therapeutic targets.
  • The Th2 subset of CD4(+) T cells and their cytokines play a crucial role in allergic inflammation.

Purpose of the Study:

  • To review recent research on chemokine receptors CCR3, CCR4, and CCR8 as therapeutic targets for allergic diseases.
  • To discuss the cellular distribution, ligands, and validation studies for these receptors.
  • To present advances in drug discovery for small molecule antagonists of these receptors.

Main Methods:

  • Review of current scientific literature on CCR3, CCR4, and CCR8 in allergic diseases.
  • Analysis of cellular expression patterns and corresponding chemokine ligands.
  • Examination of drug discovery efforts and development of small molecule antagonists.

Main Results:

  • Chemokine receptors CCR3, CCR4, and CCR8 are preferentially expressed on key allergic effector cells (Th2 cells, mast cells, eosinophils).
  • These receptors represent viable targets for therapeutic intervention in allergic diseases.
  • Significant progress has been made in developing small molecule antagonists for these chemokine receptors.

Conclusions:

  • Small molecule inhibitors targeting CCR3, CCR4, and CCR8 hold potential for treating chronic allergic diseases.
  • Antagonism of these chemokine receptors offers a strategy to inhibit inflammatory cell migration.
  • Further drug discovery advances are expected to yield effective orally bioavailable therapeutics.

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