Cell-based assays and molecular dynamics analysis of a boron-containing agonist with different profiles of binding to human and guinea pig beta2 adrenoceptors.

The design of beta2 adrenoceptor (βAR) agonists is attractive because of their wide-ranging applications in medicine, and the details of agonist interactions with βAR are interesting because it is considered a prototype for G-protein coupled receptors. Preclinical studies for agonist development have involved biological assays with guinea pigs due to a similar physiology to humans. Boron-containing Albuterol derivatives (BCADs) designed as bronchodilators have improved potency and efficacy compared with their boron-free precursor on guinea pig βARs (gpβARs), and two of the BCADs (BR-AEA and boronterol) conserve these features on cells expressing human βARs (hβARs).