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.
With the expanding importance of Beta-Arrestin-mediated signaling and the role of biased signaling in GPCR physiology, robust Beta-Arrestin assays have become a critical piece of GPCR-targeted drug development.
First generation Beta-Arrestin assays rely on tagging both the GPCR-of-interest and Beta-Arrestin with fusion proteins that when brought together mediate production of light. Multispan’s proprietary MULTISCREENTM Beta-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.
MULTISCREENTM Beta-Arrestin assays utilize the translocation of Beta-Arrestin for the assay readout, a process distinct due to the tagging of Beta-Arrestin and a membrane sensor instead of the GPCR itself. This approach facilitates closer proximity between the tagged arrestin and the membrane sensor, initiating a functional luciferase enzyme reaction.
By avoiding GPCR tagging, it sidesteps the associated drawbacks, offering a viable method to study Beta-Arrestin activation in endogenous or orphan GPCRs. This technique is designed for high throughput, cell-based screening, promising efficiency and accuracy in GPCR research.
For detailed insights, consult with our technical team or request a quote.
In the highly specialized domain of GPCR-targeted drug development, the importance of working with unmodified GPCRs cannot be overstated. Traditional Beta-Arrestin assays necessitate GPCR tagging, a process that has been shown to potentially induce deleterious receptor conformational changes, promote steric hindrance, or even alter receptor pharmacology. Such modifications not only compromise the physiological relevance of the data generated but can significantly impact the identification and optimization of highly qualified drug candidates.
Recognizing these challenges, the advanced MULTISCREENTM Beta-Arrestin Sensor Technology stands out as a reliable and precise solution. Here are the prominent ways this technology is shaping the future of GPCR research:
True Pharmacology: By enabling the assessment of GPCRs in their native form, it safeguards the integrity of receptor pharmacology, paving the way for data that mirrors the true physiological interactions more closely.
Relevance in Data: The technology allows for the assay of endogenously expressed GPCRs, ensuring that the data generated is highly relevant and reflective of the in-vivo conditions, thus enhancing the accuracy of preliminary screenings in drug development processes.
Expanding Target Pool: The MULTISCREENTM Beta-Arrestin Sensor Technology facilitates the characterization of orphan GPCRs, broadening the scope of potential targets and advancing opportunities in GPCR research and drug development.
Accelerated Drug Development: Perhaps one of the most remarkable features is its compatibility with a single cell line for conducting multiple GPCR assays. This not only streamlines the operational workflow but remarkably accelerates the pace of drug development, saving both time and resources while maintaining a high standard of reliability and efficiency.
By prioritizing unmodified GPCRs, the MULTISCREENTM Beta-Arrestin Sensor Technology stands as a formidable tool in the researcher’s arsenal, promising a revolution in GPCR-targeted drug development through enhanced efficacy and the true realization of the potentials hidden in GPCR signaling pathways.
Beta-Arrestin sensor technology is available as a portfolio of reagents, kits, and services to meet your specific assay needs:
|Receptor Family||Receptor||Species||Parental||Stable Cell Lines||Division-Arrested Cells||Membranes|
|Angiotensin||AT1||human||HEK293T β-Arrestin1||HA1417- BA1||DHA1417- BA1||MHA1417- BA1|
|Cannabinoid||CB1 MUTANT B||human||CHO-K1 β-Arrestin2||CA1513BA2-1||DCA1513BA2-1||MCA1513BA2-1|
|Citric Acid Cycle Intermediates||GPR91||human||CHO-K1 B-Arrestin2||CA1141BA2-1||DCA1141BA2-1||MCA1141BA2-1|
|Free Fatty Acid||GPR120L||human||HEK293T β-Arrestin2||CA1522||DCA1522||MCA1522|
|GPR40||cynomolgus monkey||CHO-K1 β-Arrestin2||CApc1101-1||DCApc1101-1||MCApc1101-1|
|Orphan||GPR35 (short form)||human||CHO-K1 β-Arrestin2||CA1096-1||DCA1096-1||MCA1096-1|
|GPR35 (long form)||human||CHO-K1 β-Arrestin2||CA1523-1||DCA1523-1||MCA1523-1|
|GPR35 (long form) T108M Mutant||human||CHO-K1 β-Arrestin2||CA1524-1||DCA1524-1||MCA1524-1|
|Proton-Sensing Receptors||GPR4||human||HEK293T β-Arrestin2||CA1100||DCA1100||MCA1100|
|Parental Cells||HEK293T β-Arrestin2||CA0001||MCA0001|