Recent structural advances of β1 and β2 adrenoceptors yield keys for ligand recognition and drug design.

Because they represent attractive drug targets, adrenoceptors have been widely studied. Recent progress in structural data of β-adrenoceptors allows us to understand and predict key interactions in ligand recognition and receptor activation. Nevertheless, an important aspect of this process has only begun to be explored: the stabilization of a conformational state of these receptors upon contact with a ligand and the capacity of a ligand to influence receptor conformation through allosteric modulation, biased signaling, and selectivity. The aim of the present Perspective is to identify the well-defined orthosteric binding site and possible allosteric sites and to analyze the importance of the ligand-receptor interaction in the stabilization of certain receptor conformations. For this purpose, we have reviewed recent advances made through the use of X-ray data from ligand-β-adrenoceptor (including ADRB1 and ADRB2) crystal structures. Most importantly, implications in the medicinal chemistry field are explored in relation to drug design.