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A Wide Range of Compound Efficacies Revealed Using PathHunter® Arrestin Assays

A Wide Range of Compound Efficacies Revealed Using PathHunter® Arrestin Assays
Version:
SBSP_0410

File Name/Number:
SBS 2010

Year:
2010

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DiscoveRx has developed a novel application of our established Enzyme Fragment Complementation (EFC) technology that allows us to monitor protein-protein interaction events in whole cells. Using this approach, we have designed the PathHunter® Arrestin assay that monitors arrestin binding to activated GPCRs. The activity is subsequently detected with a single addition, HTS friendly, chemiluminescent read out. β-Arrestin recruitment is a well established aspect of GPCR biology, and DiscoveRx has now successfully commercialized over 220 different cell lines for unique GPCR targets analyzed with this approach. In accord with natural biological functions in cells, the PathHunter® Arrestin assays measure the activation of receptors in a stoichiometric, one-to-one fashion, where receptor activation is reflected in a linear increase in chemiluminescent signal. This is in stark contrast to other functional assays that are amplified via signal transduction cascades where the maximum signal is dictated by rate-limiting endogenous cellular proteins. This novel property of the PathHunter® Arrestin assay makes the pharmacology independent of receptor expression levels and provides an ideal platform for accurate efficacy measurements of both agonists and partial agonists.