Look at GPCR drug discovery from a whole new angle!

The first HTS assay platform for RGS proteins

Members of the "regulator of G-protein signaling" (RGS)-protein superfamily act as "GTPase-accelerating proteins" (GAP) for heterotrimeric G-protein alpha subunits, thereby attenuating GPCR signaling. Their selectivity for specific GPCRs and downstream signaling components and their tissue-specific expression makes them attractive as potential therapeutic targets, with the potential for modulating the effects of existing GPCR agonists.

Why Screen RGS Proteins?

• They interact specifically with GPCR Galpha subunits to modulate downstream pathways.
• They have broad therapeutic potential, including CNS, cardiovascular, oncology, and metabolic diseases.
• Modulating RGS proteins may provide improved efficacy and reduced side effects for current GPCR agonists.

• Universal RGS Detection: Only HTS-ready assay method for measuring RGS GAP activity.
• Validated Assay Development: Assay development followed by reagent supply to support your internal screening projects.
• No Licensing Fee: RGScreen™ technology is transferred with reagent supply.
• Selectivity Profiling: Follow-up selectivity profiling vs. panels of RGS and/or Galpha proteins.

Unique, HTS-Validated Assay to Measure RGS Protein GAP Activity

The most direct way to detect RGS function is by measuring the increased GTPase activity of the associated Galpha protein. However, the GTPase activity of isolated Galpha proteins is limited by GDP dissociation, so RGS GAP activity cannot be measured using simple biochemical assays. The RGScreen™ platform overcomes this kinetic constraint by using proprietary Galpha protein variants with altered GTP hydrolysis and GDP dissociation rates that enable detection of RGS GAP activity using the Transcreener^® GDP Assay.

Simple Commerical Model with No Licensing or Tech Transfer Fee

We will produce and validate your RGS protein targets for the RGScreen™ platform on a simple fee-for-service basis. Next, we will provide all necessary reagents (RGS proteins, variant Galpha proteins, Transcreener^® GDP Assay) to support your internal RGS protein screening program. Lastly, if desired, we will perform selectivity profiling for your hits using panels of RGS and/or Galpha proteins. All of the RGScreen™ reagents are sold under a standard "shrink-wrap" license with no additional technology transfer or pass through fees.

Pilot Screen to identify compounds with specific effects on RGS GAP activity. Transcreener^® GDP Assay components were added to wells containing 50 nM Galphai1 (R178M/ A326S) with 250 nM RGS4 protein and 10 µM compound (in 0.5% [v/v] final concentration of DMSO), 150 µM of reactive RGS4 inhibitor CCG-4986, or 0.5% DMSO only. The range of signal observed (3 standard deviations about the mean is denoted by the dashed lines for the 960-compound library screen using RGS4 and Galphi1 (R178M/A326S) (coefficient of variation [CV%] = 8.8%).

For more information on the RGScreen™ Assay Service, please contact BellBrook Labs:
866.313.7881 in North America
info@bellbrook labs.com