Jayce Technology to decipher receptor biology and pharmacology

Traditional pharmacology posits that a ligand can be either classified as an agonist (full or partial), antagonist or inverse agonist through a specific receptor subtype, and that this characteristic will be consistent with all effector (second messenger) systems coupled to that receptor. While this dogma has been the backbone of ligand-receptor interactions for decades, recent data indicates that this classic definition of ligand-protein associations does not hold true for a number of compounds; such compounds may be termed as mixed agonists-antagonists. Functional selectivity posits that a ligand may inherently produce a mix of the classic characteristics through a single receptor isoform depending on the effector pathway coupled to that receptor. For instance, a ligand cannot easily be classified as an agonist or antagonist, because it can combine both attribute, depending on its preferred signal transduction pathways. Thus, such ligands must instead be classified on the basis of their individual effects in the cell, instead of being either an agonist or antagonist to a receptor. Actelion?s JAYCE platform generates proprietary biological information delineating beneficial and adverse signaling pathways at specific receptors, and identifies ligands that activate only the pathways associated with therapeutic benefit. The platform is a purpose-built set of integrated tools and techniques including diverse proprietary assays of GPCR function and regulation , which can predict therapeutic index and offer insights into G protein and b-arrestin-mediated mechanisms associated with pharmacological responses. These assays are aligned with biological signaling information obtained by dissecting GPCR/7TM signal transduction networks with real-time measurement. The JAYCE platform is an effective and efficient means of discovering meaningfully differentiated biased ligands targeting important clinical needs.