Utilization of PathHunter® Arrestin Cell Lines for Detection of Arrestin Biased Ligands and Compound Pharmacology Distinct from Second Messengers

Version:: SBS08
File Name/Number:: SBS 2008
Year:: 2008

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DiscoveRx has developed a panel of over 120 characterized GPCR cell lines that monitor receptor activity using interaction with human β-Arrestin. These cell lines have numerous applications in both high throughput screening and downstream compound analysis, and have now been successfully adopted by a number of pharmaceutical and biotechnology companies. A relatively recent application for these cell lines has been analysis of compounds for arrestin ligand bias. We have demonstrated that the cells can be used to detect arrestin biased compounds for two example GPCRs, providing additional value for this product panel. As these cells have been used more frequently in profiling applications, we have identified a number of examples where the compound pharmacology is distinct with an arrestin readout compared to more traditional second messenger assays. We will present specific examples where compounds have shown unique pharmacology when analyzed with arrestin. Taken together, the results here suggest that arrestin is a valuable, complementary technology for analysis of GPCR function and indicate that some receptors may merit analysis with both arrestin and more traditional second messenger approaches to obtain a complete understanding of compound function.