Discovery of Novel G-Protein or Arrestin-Biased Ligands Using a Suite of GPCR Signaling Platforms
As more is learned about the intricacies of GPCR signaling, the harder it becomes to accurately describe ligand activity using a single functional readout. It is now well appreciated that GPCR activation results in G-protein dependent as well as G-protein independent signaling events such as β-arrestin recruitment and internalization. The complex relationship that exists between G-proteins and β-Arrestin signaling determines both the efficacy and potential side effects of GPCR-targeted drugs. Therefore, quantitatively examining these pathways can aid in defining compound function and can lead to the discovery of novel biased ligands with unique attributes. DiscoveRx® has developed a suite of assays designed to detect GPCR signaling through second messenger activation, Arrestin binding, and receptor internalization. These assays can be used in parallel as a simple, rapid, and quantitative approach to discover novel, biased ligands with unique attributes that could result in greater therapeutic efficacy and more favorable side effect profiles.