A Focus on Unusual ECL2 Interactions Yields β2‐Adrenergic Receptor Antagonists with Unprecedented Scaffolds
Copyright policy )A Focus on Unusual ECL2 Interactions Yields β2‐Adrenergic Receptor Antagonists with Unprecedented Scaffolds
AbstractThe binding pockets of aminergic G protein‐coupled receptors are often targeted by drugs and virtual screening campaigns. In order to find ligands with unprecedented scaffolds for one of the best‐investigated receptors of this subfamily, the β2‐adrenergic receptor, we conducted a docking‐based screen insisting that molecules would address previously untargeted residues in extracellular loop 2. We here report the discovery of ligands with a previously undescribed coumaran‐based scaffold. Furthermore, we provide an analysis of the added value that X‐ray structures in different conformations deliver for such docking screens.
- University of Copenhagen Denmark
- ETH Zurich Switzerland
- University of Copenhagen Denmark
- INTERAX BIOTECH AG Switzerland
- University of Copenhagen Denmark
Virtual screening, AGONISTS, drug design, Beta2-adrenergic receptor ligand, Drug design, Structure-Activity Relationship, G protein-coupled receptors, CHEMISTRY, Adrenergic beta-2 Receptor Antagonists, Humans, ASSAY, DOCKING, G protein-coupled receptor, IDENTIFICATION, Dose-Response Relationship, Drug, Molecular Structure, STRUCTURAL INSIGHTS, Full Papers, virtual screening, EFFICACY, DRUG DISCOVERY, Molecular Docking Simulation, SELECTIVITY, ligand scaffolds, beta(2)-adrenergic receptor ligands, LIGANDS, Ligand scaffold, Beta2-adrenergic receptor ligand; Drug design; G protein-coupled receptor; Ligand scaffold; Virtual screening, Receptors, Adrenergic, beta-2
Virtual screening, AGONISTS, drug design, Beta2-adrenergic receptor ligand, Drug design, Structure-Activity Relationship, G protein-coupled receptors, CHEMISTRY, Adrenergic beta-2 Receptor Antagonists, Humans, ASSAY, DOCKING, G protein-coupled receptor, IDENTIFICATION, Dose-Response Relationship, Drug, Molecular Structure, STRUCTURAL INSIGHTS, Full Papers, virtual screening, EFFICACY, DRUG DISCOVERY, Molecular Docking Simulation, SELECTIVITY, ligand scaffolds, beta(2)-adrenergic receptor ligands, LIGANDS, Ligand scaffold, Beta2-adrenergic receptor ligand; Drug design; G protein-coupled receptor; Ligand scaffold; Virtual screening, Receptors, Adrenergic, beta-2
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