A pluridimensional view of biased agonism

摘要: When studying G protein-coupled receptor (GPCR) signaling and ligand-biased agonism, at least three dimensional spaces must be considered, as follows: 1) the distinct conformations that can stabilized by different ligands promoting engagement of effectors accessory regulators; 2) subcellular trafficking conferred ligands, which results in spatially signals; 3) differential binding kinetics maintain specific conformation and/or localization for periods time, allowing effector subsets. These pluridimensional aspects contribute to faces functional selectivity provide a complex, interconnected way define profile each individual ligand acting GPCRs. In this review, we discuss how these may diversity signaling, but also they shed light on complexity data analyses interpretation. The impact phenotype variability source diversity, influence novel more sensitive assays detection analysis pluridimensionality, is discussed. Finally, perspectives use concept drug discovery, highlight future predictive tools facilitate identification compounds with optimal therapeutic safety properties based signatures candidates.