Topic Overview:

G-protein-coupled receptors (GPCRs) are important cell surface receptors that constitute about 30-40 percent of current drug targets. Recent progress in GPCR structural biology over the past several years has allowed visualization of multiple behaviors of GPCR ligands with various pharmacological properties, which has revolutionized the understanding of GPCR pharmacology. In Zhang’s lecture, he will focus on two GPCRs, human protease-activated receptor 1 (PAR1) and β2-adrenergic receptor (β2AR), and discuss the molecular basis for the action of two drugs targeting these receptors—a newly approved antiplatelet drug vorapaxar as PAR1 antagonist and a widely used asthma drug salmeterol as β2AR agonist. He will also talk about his structure-based drug development effort on β2AR based on the β2AR-salmeterol crystal structure, which has led to the discovery of novel allosteric ligands for β2AR.