MultiScreen™ Beta-Arrestin Sensor Technology
High Throughput Detection of Biased Cell Signaling by Unmodified GPCRs
The First HTS β-Arrestin Assay for Native GPCRs in Recombinant or Primary Cells
- No GPCR tagging required – assess true receptor pharmacology
- No wash, homogeneous assay in 96- or 384-well microplate formats
- Fully validated for transiently or stably transfected cells
- No GRK2 co-transfection required
- Available as assay kits, reagents, cell lines, and services
CHO-K1 cells stably expressing the µ opioid receptor were stimulated with known agonists and the MultiScreen β-arrestin assay run in a 384-well format.
Developing Candidates with Improved Efficacy & Safety Profiles
With the expanding importance of β arrestin-mediated signaling and the role of biased signaling in GPCR physiology, robust β-arrestin cell-based assays have become a critical piece of GPCR -targeted drug development.
First generation β-Arrestin assays rely on tagging both the GPCR-of-interest and β-arrestin with fusion proteins that when brought together mediate production of light. Multispan’s proprietary MultiScreen β-Arrestin sensor technology relies on unmodified GPCRS and thus overcomes receptor-tagging drawback of first-generation technologies, enabling high-throughput detection of beta-arrestin translocation induced by native GPCRs in vitro and in vivo.
MultiScreen β-Arrestin Assays –The Next Generation
MultiScreen β-Arrestin assays use translocation of β-arrestin as the assay readout; however, it is β-arrestin and a membrane ‘sensor’ that are tagged rather than the GPCR of interest. Upon recruitment, tagged arrestin comes within proximity of a membrane sensor which in turns results in a functional luciferase enzyme.
This scheme overcomes receptor tagging drawbacks and importantly offers a means to examine β-arrestin activation via
endogenous or orphan GPCRs using an assay format well suited for high throughput, cell-based screening.
Why are Unmodified GPCRs so Important?
GPCR tagging, required by other β-Arrestin assays can be deleterious, induce receptor conformational changes, lead to
steric hinderance, or modify receptor pharmacology – all of which impact the identification and optimization of highly
qualified drug candidates. MultiScreen β-Arrestin Sensor Technology enables researchers to:
- Assess GPCRs in their native form for true pharmacology
- Assay endogenously expressed GPCRs for more relevant data
- Characterize orphan GPCRs to expand your target pool
- Use a single cell line for multiple GPCR assays for accelerated drug development
MultiScreen™ β-Arrestin Assay Solutions
β-arrestin sensor technology is available as a portfolio of reagents, kits, and service to meet your specific assay needs:
- MultiScreen™ β-Arrestin reagent options
- HSV and Bacmam viral particles carrying MultiScreen™ β-Arrestin sensor genes
- β-Arrestin sensors plasmids
- MultiScreen™ β-Arrestin Assay Kits (Catalog MSBAK01)
- MultiScreen™ β-Arrestin BacMam or HSV Assay Kits (Catalog MSBAKBM01-1, MSBAKHSV01-1)
- Cell Lines
- HEK293 and CHO parental cell lines stably expressing MultiScreen™ β-Arrestin sensors
- 20+ GPCR stable cell lines co-expressing β-Arrestin sensor
- > 1000 GPCR-expressing cell lines
- Custom stable cell line generation co-expression β-Arrestin sensor and GPCR
- Development of MultiScreen™ β-Arrestin HTS assays
- GPCR screening and profiling services using β-Arrestin assays
MultiScreen™ β-Arrestin Assay Protocols: