MULTISCREEN™ GPCR β-Arrestin Solutions

An academic lab is in need to generate publication quality data for just a couple of tool molecules in the β-Arrestin cell signaling pathway. Instead of the older β-Arrestin technologies that they already have in the lab, they choose to examine their molecules using our new MULTISCREEN™ β-Arrestin Sensor, to avoid tagging their GPCR that may skew its pharmacology. Since the lab already has a stable cell line expressing the GPCR validated in the cAMP assay, they can purchase just the MULTISCREEN™ β-Arrestin BacMam Assay Kit. After simply adding the viral particles to the cell culture, 24-48 hours later,  they will be able to measure both signaling pathways in the one cell line using the substrate included in the kit, without having to modify their receptor. The assay is mix-and-read, no-wash, and homogeneous. It takes 30 minutes total with less than 10-minute hands-on time.  The same viral delivery assay kit can also be applied to primary cells for similar purposes. If the academic lab does not have any cell line expressing their GPCR target, they can purchase Multispan’s division-arrested cells expressing both the GPCR and the β-Arrestin Sensor instead or just the GPCR target alone plus the β-Arrestin BacMam Assay Kit. All these solutions are fast, convenient and reasonably priced at a standard reagent rate, amenable for academic budget.

In contrast, a pharmaceutical company with an orphan GPCR could be an example at the other end of the spectrum. Because very little biology is known, our team of experts will get involved early by studying the receptor in both β-Arrestin and cAMP pathways using transient transfection. Based on these initial results, we will generate and select stable cell lines co-expressing both the orphan GPCR and the β-Arrestin Sensor. We will determine the best clone to use for surrogate ligand screening based on baseline activity level and carry out the HTS screening campaign. The surrogate ligand candidate may be further studied in alternative clones to select the best clone for compound lead optimization. Combined with Multispan’s assay expertise-driven service, the MULTISCREEN™ β-Arrestin Sensor can be a powerful tool in deciphering the biology of orphan GPCRs and discovering novel therapeutics by utilizing these untapped, mysterious but highly “druggable” receptors.