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Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
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Knowledge-based analysis of multi-potent G-protein coupled receptors ligands
Patricia Faure1, Elodie Dubus, Ismail Ijjaali
1Aureus-Pharma, 174 Quai de Jemmapes, 75010 Paris, France. patricia.faure@aureus-pharma.com
European Journal of Medicinal Chemistry
|October 12, 2010
Summary
Researchers found few drugs targeting multiple G-protein coupled receptor (GPCR) classes. Most multi-target GPCR drugs interact within Class A, often between amine and peptide receptor clusters.
Area of Science:
- Pharmacology
- Medicinal Chemistry
- Drug Discovery
Background:
- G-protein coupled receptors (GPCRs) are a major drug target class.
- Many GPCRs have known ligands, but some drugs interact with multiple targets.
- GPCRs are classified into Classes A, B, and C based on sequence and pharmacology.
Purpose of the Study:
- To identify compounds that interact with multiple GPCRs from different classes or subclasses.
- To analyze the prevalence of multi-target GPCR ligands in scientific literature and patents.
Main Methods:
- Literature and patent database search for GPCR-interacting compounds.
- Classification of GPCR targets into main classes (A, B, C) and pharmacological clusters.
- Analysis of identified compounds for multi-target activity across different GPCR classes and clusters.
Main Results:
- A limited number of compounds were found to interact with GPCRs from different main classes (A/B, A/C).
- No compounds were identified acting on both Class B and Class C GPCRs.
- Within Class A, cross-reactivity was observed, particularly between amine and peptide receptor clusters.
Conclusions:
- Multi-target GPCR drugs are less common than anticipated, especially those acting across different major receptor classes.
- Drug development targeting multiple GPCRs, particularly within Class A, presents opportunities and challenges due to cross-reactivity.
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