BellBrook Labs Unveils Novel GPCR Screening Approach Based on RGS Protein Interactions

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BellBrook Labs has developed a new HTS assay for screening the “Regulators of G-protein Signaling” (RGS) proteins that influence signaling of G Protein-Coupled Receptors (GPCRs), an important class of proteins for the treatment of multiple diseases, such as cancer, cardiovascular disease, inflammation, and CNS disorders. Offered as an assay development service, the RGScreen™ Assay Service opens up new therapeutic strategies for modulating GPCR pathways, including the potential to fine-tune the effects of existing GPCR ligands.

RGScreen™ Assay

RGScreen™ Assay platform uses proprietary Gα protein variants that enable direct detection of RGS catalytic activity using the Transcreener® GDP Assay.

BellBrook Labs today introduced an innovative approach to GPCR screening through the launch of its RGScreen™ Assay Service. GPCRs, a large family of transmembrane receptors, are the most extensively validated class of therapeutic targets. RGS proteins attenuate GPCR signals by increasing the GTPase activity of associated Gα proteins. Though they have been the focus of intense investigation as potential drug targets, the lack of suitable HTS assay methods has prevented large scale screening efforts. BellBrook overcame this technical hurdle by developing proprietary Gα variant proteins that enable direct detection of RGS catalytic activity using their Transcreener® HTS Assay platform.

The discovery of RGS proteins and their ability to attenuate GPCR signals opened up a new avenue for modulating the activity of GPCR ligands. The exploitation of this opportunity requires robust HTS assay methods. The most direct way to detect RGS function is by measuring the increased GTPase activity of the associated Gα protein. However, GTPase activity of isolated Gα proteins is limited by GDP dissociation, so RGS GAP activity cannot be measured using simple biochemical assays. The BellBrook team, collaborating with Dr. David Siderovski, a co-discoverer of the RGS protein family at the University of North Carolina-Chapel Hill School of Medicine, overcame this kinetic constraint by creating Gα protein variants with altered GTP hydrolysis and GDP dissociation rates that enable detection of RGS GAP activity using the Transcreener® GDP Assay. The innovative approach was described in a 2009 publication in the Journal of Biomolecular Screening. The RGScreen™ Assay Service provides custom assay development to produce and validate desired RGS protein targets followed by ongoing reagent supply, including RGS proteins, variant Galpha proteins, and Transcreener® GDP Assay components, to support large scale RGS protein screening programs.

About BellBrook Labs. BellBrook Labs, LLC develops detection reagents and microfluidic devices that accelerate the discovery of more effective therapies for cancer and other debilitating diseases. Transcreener® is a patented high throughput screening assay platform that was introduced in 2005 and is used to identify inhibitors for kinases and other types of protein drug targets. The iuvo™ Microconduit Array technology is a line of unique microscale devices for miniaturization and automation of advanced cell models that are more representative of human physiology. Visit BellBrook’s website for more information: http://www.bellbrooklabs.com.

Contact us at 866.313.7881 or info(at)bellbrooklabs(dot)com for more information.

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Robert Lowery
BellBrook Labs
(608) 443-2400
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