Discovery of Short-Acting β2-Adrenergic Receptor Agonists Based on Computational Methods
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Graphical Abstract
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Abstract
G protein-coupled receptors constitute a crucial superfamily of membrane proteins that play a pivotal role in cellular signal transduction and serve as primary targets in contemporary drug development. The β2-adrenergic receptor, a representative member of class A G protein-coupled receptors, is a critical target in the therapeutic management of respiratory diseases. Despite the availability of several β2-adrenergic receptor agonists in clinical practice, there remains a substantial need for optimization concerning drug safety, efficacy, and receptor selectivity. In this study, a virtual screening approach was utilized to effectively identify β2-adrenergic receptor agonists from a compound library comprising 19 million molecules. Through comprehensive cellular assays and in vivo pharmacokinetic evaluations, a novel short-acting agonist with an EC50 value of 0.86 nmol/L was discovered, presenting a promising candidate for the development of next-generation treatments for respiratory diseases.
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