In Vitro Pharmacology >> GPCRs >> Functional

GPCR Screening and Profiling with Functional Assays

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Cell-based assays for GPCRs

When assessing a GPCR therapeutic's potential efficacy and liabilities, it is important to understand its on and off target activity. GPCRs can signal through a variety of cascades and a drug will activate, inhibit, or modulate one or more of these. Indeed, compound activity can be complex as certain compounds may elicit different activity on different signaling cascades, also known as ligand biased signaling. Eurofins has services covering several second messenger pathways to better understand compound activity. Along with binding assays, these functional assays can provide a complete profile of a compound's in vitro pharmacology.

GPCRProfiler® services is the first complete cell-based functional GPCR profiling platform that uses a common validated readout for over 165 GPCRs. The foundation of GPCRProfiler® is our ChemiScreen™ GPCR stable cell lines that are used for real-time calcium flux assays to rapidly, reliably, and reproducibly screen and profile compounds. Using one platform allows ligands to be screened for agonist and antagonist activity using identical buffer conditions and incubation times for the entire spectrum of GPCRs for easy high throughput analysis and comparison.

Our cell based assays feature multiple second messenger readouts, including cAMP for Gi and Gs coupled receptors as well as IP1 and IP3/calcium flux for Gq coupled receptors, emphasizing the natural pathway of the receptor. Additionally, we also have label free cell based assays to look at endogenous receptor signaling as well as traditional GTPγS assays.

Together, our collection of functional assays, along with our binding studies, can provide an orthogonal approach to confirm the in vitro pharmacology of your compounds.

Advantages of our functional assay services:

  • Multiple assays formats to choose from: calcium flux, cAMP, IP3/IP1, GTPγS and label free
  • Determine full, partial or inverse agonist and antagonist activity
  • Single concentration screening or dose response for EC50 and IC50 determination
  • Over 165 of targets covered in >445 assays
  • A la cart selection and a variety of standard panels to choose from
  • Industry standard instrument platforms: FLIPRTETRA®, EnVision® and CellKey™
  • Experience: first company to provide outsourced cell based GPCR assays in 2006
  • All cell lines produced in-house
  • Quick turnaround times of 1-3 weeks depending on project types



Figure 1. GPCRProfiler™ Selectivity Profiling

Dose response studies determined potency and efficacy of A) clozapine (atypical antipsychotic) and B) oxymetazoline (nasal decongestant) on multiple receptors. Clozapine demonstrated non-selectivity for biogenic amine receptors. Oxymetazoline had a broad spectrum of functionality (antagonist, full or partial agonist) depending on the receptor examined.