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Updated: Jun 9, 2026
09:44
High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
Pathway-specific, species, and sub-type counterscreening for better GPCR hits in high throughput screening
Robert Swanson1, James R Beasley
1Ligand Pharmaceuticals, 3000 Eastpark Blvd., Cranbury, NJ 08512, USA.
Current Pharmaceutical Biotechnology
|September 3, 2010
Summary
Early assessment of G protein-coupled receptor (GPCR) modulators for signaling and species selectivity can save time and cost in drug discovery. Evaluating selectivity during high-throughput screening is key for efficient development.
Area of Science:
- Pharmacology
- Drug Discovery
- Molecular Biology
Background:
- G protein-coupled receptors (GPCRs) are a major class of drug targets.
- Identifying selective modulators is crucial for effective drug development.
- Early screening can prevent costly late-stage failures.
Purpose of the Study:
- To highlight the importance of assessing GPCR modulator selectivity early in drug discovery.
- To demonstrate how signaling pathway, species, and family member selectivity can be evaluated.
- To advocate for incorporating selectivity assessments into high-throughput screening.
Main Methods:
- Review of existing screening strategies for GPCR modulators.
- Examples of how selectivity assays have been integrated into screening.
- Analysis of the benefits of early selectivity profiling.
Main Results:
- Early assessment of signaling pathway selectivity can guide lead optimization.
- Species selectivity screening is vital for predicting in vivo efficacy.
- Profiling against related GPCRs minimizes off-target effects.
Conclusions:
- Integrating selectivity assessments into early-stage screening, including high-throughput screening, is essential for efficient GPCR drug discovery.
- This approach can significantly reduce development time and costs.
- Optimizing selectivity early leads to safer and more effective therapeutics.
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