Defining Structure-Functional Selectivity Relationships (SFSR) for a Class of Non-Catechol Dopamine D₁ Receptor Agonists.

ABSTRACT: G protein-coupled receptors (GPCRs) are capable of downstream signaling through distinct noncanonical pathways such as β-arrestins in addition to the canonical G protein-dependent pathways. GPCR ligands that differentially activate the downstream signaling pathways are termed functionally selective or biased ligands. A class of novel non-catechol G protein-biased agonists of the dopamine D₁ receptor (D₁R) was recently disclosed. We conducted the first comprehensive structure-functional selectivity relationship study measuring G_S and β-arrestin2 recruitment activities focused on four regions of this scaffold, resulting in over 50 analogs with diverse functional selectivity profiles. Some compounds became potent full agonists of β-arrestin2 recruitment, while

SUBMITTER: Martini ML 

PROVIDER: S-EPMC6688508 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature