Assessment of biased agonism at the A adenosine receptor using β-arrestin and miniGα recruitment assays.

The A adenosine receptor (AAR) is a G protein-coupled receptor that is involved in a wide variety of physiological and pathological processes, such as cancer. However, the use of compounds pharmacologically targeting this receptor remains limited in clinical practice, despite extensive efforts for compound synthesis. Moreover, the possible occurrence of biased agonism further complicates the interpretation of the functional characteristics of compounds.

Probing structure-activity relationship in β-arrestin2 recruitment of diversely substituted adenosine derivatives.

In the adenosine receptor (AR) subfamily of G protein-coupled receptors (GPCRs), biased agonism has been described for the human AAR, AAR and AAR. While diverse AAR agonists have been evaluated for receptor binding and G-mediated cAMP signalling, the β-arrestin2 (βarr2) pathway has been left largely unexplored. We screened nineteen diverse adenosine derivatives for βarr2 recruitment using a stable hAAR-NanoBit-βarr2 HEK293T cell line.