A pathway-selective adenosine A1 receptor ligand

摘要

The adenosine A, receptor (A1AR) is an important target for cardioprotection, but current A1AR drugs are Limited for this indication because of the occurrence of bradycardia as a major adverse effect mediated by the same receptor. To address this problem, researchers at Monash University designed a Ligand that simultaneously bridges two different sites on the A1AR, based on the hypothesis that this bitopic mode would result in unique receptor conformations that could signal to desirable pathways while avoiding pathways mediating undesirable effects (Valant C, May L.T., Aurelio L, Chuo C, White P.J., Baltos J., Sexton P.M., Scammells P.J., Christopoulos A. Proc. Natl Acad. Sci, USA 2014, 111, 4614-19).