GPCRs Assays

G protein-coupled receptors (GPCRs), also known as 7TM receptors, constitute the largest superfamily of cell surface receptors. These receptors play key roles in regulation of a wide variety of physiological processes, including cognition, metabolism, inflammation, immunity and cell proliferation, as well as development. Despite the large number of GPCRs that are available as potential drug targets, currently approved drugs only address a small portion of the known receptors; many GPCRs remain uncharacterized. Thus, this target class remains an area of strong interest in drug discovery.

Figure 1 GPCR Signaling Pathway

• Binding Assays

CD ComputaBio provides GPCR radioligand binding assays for different targets. Gold standard filtration assays are conducted with an agonist or antagonist at a single concentration or a dose response for IC₅₀ determination.

• Functional Assays

GPCR functional assays that cover multiple second messenger pathways are available. These include cAMP for Gi and Gs coupled receptors, IP1 and IP3/calcium flux for Gq coupled receptors, label free assays for endogenous signaling and traditional GTPγS assays. Agonist and antagonist assays are available in single or dose response for EC₅₀ and IC₅₀ determination.

It is important to understand GPCR's on-and-off target activity, when assessing the potential efficacy and liabilities of GPCR therapeutics. Methods to measure GPCRs come in many forms- In addition to measures of direct ligand binding, many are indirect assays that measure events proximal to binding the represent different signaling pathways- these include reporter assays, cAMP quantitation, β-Arrestin recruitment, IP3 measurements and calcium flux to name a few. GPCR screening and profiling assays from CD ComputaBio provide the most comprehensive cell-based assay offering along with the fastest turnaround time in the industry for rapid efficacy, potency, and selectivity determination during SAR and Lead Optimization.