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Updated: May 7, 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
Technology combination to address GPCR allosteric modulator drug-discovery pitfalls
Drug Discovery Today. Technologies
|September 21, 2013
Summary
Novel allosteric modulators (AMs) targeting G-protein-coupled receptors (GPCRs) are challenging to discover. Combining FRET and BRET technologies offers a new approach to identify biased AMs effectively.
Area of Science:
- Pharmacology
- Biochemistry
- Molecular Biology
Background:
- Allosteric modulators (AMs) offer a novel therapeutic strategy for targeting G-protein-coupled receptors (GPCRs).
- Standard functional assays face challenges in identifying and characterizing AMs due to context-dependent phenomena.
Purpose of the Study:
- To develop and validate a novel technological approach for efficient discovery of biased allosteric modulators (AMs).
- To overcome limitations in current GPCR screening processes for AM identification.
Main Methods:
- Utilized a combination of Fluorescence Resonance Energy Transfer (FRET)-based library filtering.
- Employed Bioluminescence Resonance Energy Transfer (BRET)-based multiparametric compound profiling.
Main Results:
- The integrated FRET and BRET approach demonstrated effectiveness in overcoming limitations of standard GPCR screening.
- This novel methodology simplifies the discovery process for biased AMs.
Conclusions:
- Combining FRET and BRET technologies provides a powerful platform for identifying biased allosteric modulators of GPCRs.
- This approach enhances the efficiency and accuracy of GPCR drug discovery.
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