Related Experiment Video
Updated: Jul 13, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology
Katie Leach1, Patrick M Sexton, Arthur Christopoulos
1Drug Discovery Biology Laboratory, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia.
Abstract:
The past decade has witnessed a dramatic increase in the identification of allosteric modulators of G-protein-coupled receptor (GPCR) activity. Concomitantly, several new perspectives and hypotheses regarding the way ligands regulate GPCR signalling have also emerged. Here, we briefly discuss how the concepts of collateral efficacy and permissive agonism-antagonism intersect the field of allosteric GPCR modulation. Despite the challenges associated with detecting and quantifying the myriad of possible allosteric effects on GPCR activity, it is proposed that allosteric ligands offer the exciting prospect of engendering stimulus-bias in orthosteric ligand signalling, thus paving the way for not only receptor-selective but also signalling-pathway-selective therapies.
More Related Videos
Related Concept Videos
GPCRs Regulate Adenylyl Cylase Activity
Two...
GPCR Desensitization
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical, 7TM, or...
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with one...

