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Updated: May 29, 2026
07:41
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Overview of receptor allosterism
Karen J Gregory1, Patrick M Sexton, Arthur Christopoulos
1Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Victoria, Australia.
Current Protocols in Pharmacology
|September 22, 2011
Summary
G protein-coupled receptors (GPCRs) have allosteric sites that offer unique therapeutic potential. Understanding these allosteric effects on GPCR binding and signaling is crucial for drug development.
Area of Science:
- Pharmacology
- Molecular Biology
- Biochemistry
Background:
- G protein-coupled receptors (GPCRs) possess distinct allosteric sites alongside orthosteric sites.
- Allosteric sites bind small molecules and proteins, modulating receptor activity.
- Allosteric agonists can activate GPCRs independently of orthosteric ligands.
Purpose of the Study:
- To provide an overview of GPCR allosterism.
- To discuss pharmacological approaches for studying allosteric effects.
- To highlight the therapeutic potential of allosteric sites.
Main Methods:
- Review of existing literature on GPCR allosterism.
- Discussion of pharmacological techniques for characterizing allosteric modulation.
- Analysis of allosteric ligand binding and signaling events.
Main Results:
- Allosteric site binding induces conformational changes affecting orthosteric ligand interactions.
- Allosteric sites enable novel selectivity and signaling pathways.
- Quantifying diverse allosteric effects remains a significant challenge.
Conclusions:
- GPCR allosteric sites represent promising therapeutic targets.
- Pharmacological characterization is key to understanding and exploiting allosteric mechanisms.
- Further research is needed to fully quantify allosteric modulation for drug discovery.
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