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Updated: May 31, 2026
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Pharmacological modulation of chemokine receptor function
D J Scholten1, M Canals1, D Maussang1
1Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Science, VU University Amsterdam, Amsterdam, the Netherlands.
British Journal of Pharmacology
|June 25, 2011
Summary
Chemokine receptors are key targets for immune diseases. This review explores small molecules, peptides, and antibodies modulating these receptors, including allosteric mechanisms and computer-assisted modeling for drug development.
Area of Science:
- Pharmacology
- Immunology
- Structural Biology
Background:
- G protein-coupled chemokine receptors and their ligands are implicated in diverse immune-related diseases.
- Small-molecule chemokine receptor antagonists are actively pursued for therapeutic development.
- Market-approved drugs like AMD3100 (CXCR4) and Maraviroc (CCR5) highlight the therapeutic potential.
Purpose of the Study:
- To review evidence for modulating chemokine receptors with various ligands.
- To discuss computer-assisted modeling of chemokine receptor-ligand interactions.
- To consider functional selectivity and receptor dimerization in drug design.
Main Methods:
- Review of existing literature on chemokine receptor modulators.
- Analysis of recent G protein-coupled receptor crystal structures.
- Integration of mutagenesis and pharmacological studies.
Main Results:
- Small-molecule ligands often exhibit allosteric modes of action, deviating from simple competition.
- Evidence supports modulation of chemokine receptors by small molecules, peptides, and antibodies.
- GPCR crystal structures and computational modeling enhance understanding of ligand interactions.
Conclusions:
- Chemokine receptors represent promising therapeutic targets for immune-related diseases.
- Allosteric modulation and understanding receptor interactions are crucial for developing novel therapeutics.
- Functional selectivity and receptor dimerization offer new avenues for targeted drug discovery.
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