Eurofins Discovery offers solutions to the challenge and expense of developing and validating robust and target-specific assays to successfully identify valuable hits targeting GPCRs while rapidly evaluating their efficacy, potency, selectivity, and safety profiles, which can take months to complete. To meet these challenges, Eurofins’ GPCR experts have developed a comprehensive range of testing services, amenable to screening and profiling studies, for efficient preclinical hit generation.
Benefit from the most comprehensive GPCR assay collection in the industry to design and execute optimal screening cascades and saves months of assay development and testing time.
- Access over 2,750 off-the-shelf and fully validated GPCR-specific biochemical and cell-based assays and products
- Use a breadth of approaches to identify active compounds and allosteric modulators, including radio-ligand binding, β-arrestin recruitment, cAMP, IP-1 or calcium second messenger assays, internalization / trafficking assays and biophysical approaches
- Select the optimal technology for diverse readout needs, such as radioactive, fluorescence, luminescence, TR-FRET and FP assays, and for label-free biophysical readouts such as MS, SPR, and microscale thermophoresis (MST)
- Gain access to compound screening collections with Diversity or GPCR-focused libraries for immediate incorporation into an HTS campaign; as an option, include your client-supplied library
- Screen up to 50k – 100k+ compounds per week with acoustics platforms for compound dispensing and reformatting, and automated robotic systems for efficient compound screening
- Reduce downstream attrition rates with proprietary platforms such as BioMAP® Diversity Early Screening for orthogonal assessments as well as selectivity, ADME, and safety pharmacology testing (in safety panels such as SafetyScreen44)
See how Eurofins experts can successfully support you in achieving rapid screening and profiling campaigns in your GPCR-targeting drug discovery programs.
Choose the Best Molecules for Preclinical and Clinical Study
Figure 1: A Typical High Throughput Screening Cascade For a CNS Program Using Eurofins Discovery GPCR Portfolio.
Figure 2: A Typical Screening Cascade Developed for Hit to Lead GPCR Program.
Over 600 cell-based assays for human and non-human orthologue GPCRs are available in multiple direct functional or biochemical readouts and offered as individual assays or in panel formats as in the table below.
| Type of services targeting GPCRs | Brief Description | Assays and Modes Available | Formats Offered | Standard TAT | Customization Possibilities |
|---|---|---|---|---|---|
| GPCR Binding Assays | |||||
| Radiometric binding assay | Competitive radioligand binding assays | > 130 assays offered covering 111 targets | From stand-alone assays (1 Dose and DRCs for IC50 and Ki determination) to MTS campaigns or profiling solutions | 15 Days | Yes (e.g. allosteric modulation of orthosteric ligand binding, kon/koff binding kinetics, tailored assay developments from client’s radioligand or cells, non-human ortholog assays…) |
| GPCR Functional Assays | |||||
| IP1 assays and Ca++ assays | Largest range of functional assays to investigate IP-1 and Ca2+ GPCR-related pathways (Gq and Gα15) | > 200 assays (agonist & antagonist modes) for over 100 targets | TR-FRET/HTRF, Fluo-4 and Fluo-8
Available for 1 Dose and/or DRC for EC50 / IC50 determination, compound combination and PAM studies. |
15-20 days | Yes (e.g. custom ligand and assay conditions, PAM studies, GPCR hit finding cascades…) |
| cAMP assays | Screening and profiling of your compounds to investigate cAMP modulation (Gi and Gs) | > 110 tests (agonist & antagonist) mode for over 75 targets | TR-FRET/HTRF assays compatible with HTS campaigns and profiling programs (1 Dose and/or DRC for EC50 / IC50 determination) | 15-20 days | Yes (e.g. Custom ligand and assay conditions, PAM studies, HTS programs…) |
| GTPgammaS functional assays | Determination of the binding of the non-hydrolyzable analog [35S]GTPγS to Gα subunits. GTPγS assays evaluate an early event after GPCR activation and are able to discriminate full or partial agonists, neutral antagonists, inverse agonists, allosteric regulators | > 95 assays covering over 30 targets (agonist, inverse agonist & antagonist modes) | Detection by scintillation for stand-alone to MTS and profiling methods. Dose response format at 8 concentrations in duplicate | 20 days | Yes, custom ligand, custom assay condition, compound combination and PAM study |
| GPCR Functional Assays using EFC β-arrestin cells | |||||
| β-arrestin recruitment assays (Enzyme Fragment Complementation technology) |
Assays utilize β-arrestin recruitment to rapidly, reproducibly and reliably profile compounds in a G-protein independent pathway. | > 336 Assays offered in Agonist, Antagonist, PAM and NAM mode. Some assays offered in Inverse Agonist mode | Primary screening at one or more concentrations. Dose response format at 10 concentrations in duplicate. Assays are also available for HTS screens |
15 days | Yes, custom ligand, custom buffer and EC50 shift |
| cAMP assays (Enzyme Fragment Complementation technology) |
HitHunter® cAMP assays are competitive immunoassays that utilize EFC. Beta arrestin assays can also be used to monitor cAMP levels by TR-FRET. | > 390 Assays are offered in Agonist, Antagonist, PAM and NAM modes | Yes, custom ligand, custom buffer, EC50 shift, choice of using HitHunter or TR-FRET format | ||
| GPCR Internalization (Enzyme Fragment Complementation technology) |
GPCR Internalization Assays are functional cell-based assays that measure GPCR endocytosis using β-arrestin cells | > 298 Assays measure total internalization or activated internalization | Primary screening at one or more concentrations. Dose response format at 10 concentrations in duplicate | 15 days | Yes, custom ligand or custom buffer |
| gpcrMAX panels (Enzyme Fragment Complementation technology |
Largest panel of gpcr assays offered in β-arrestin format | 336 Assays | Panel offered to measure agonist and antagonist activity at one concentration duplicate. | 20 days | Please inquire |
| orphanMAX panel (Enzyme Fragment Complementation technology) |
Largest panel of orphan gpcr assays offered in β-arrestin format | 73 Assays | Panel offered to measure agonist activity at one concentration duplicate. | 20 days | Please inquire |
| obesityLITE Panel | Panel of GPCR β-arrestin or second messenger assays and cytokine assay that can be used to measure specificity or selectivity during Hit to Lead or Lead Optimization stages of drug development. | 25 Assays (agonist or antagonist mode) | Panel offered to measure agonist or antagonist activity in Dose response format at 10 concentrations in duplicate | 20 days | Counter Screen assays for customization available. Please inquire |
| Peptide Hormone Class B Panel | Panel of GPCR second messenger assays that can be used to measure specificity or selectivity during Hit to Lead or Lead Optimization stages of drug development | 20 Assays in agonist mode | Panel offered to measure agonist activity in dose response format at 10 concentrations in duplicate | 20 days | Counter screen assays for customization available. Please inquire |
| gpcrBIAS (Enzyme Fragment Complementation technology) |
Compound profiling using second messenger, β-arrestin or internalization assays from a choice of > 150 GPCRs. Any two assay systems are chosen to measure bias | > 150 Assays | Dose response curves are performed in quadruplicate to measure GPCR responses for any two assay systems. Assay choices include 2nd messenger signaling, β-Arrestin recruitment, and receptor internalization. Experiments with the natural ligand and test substance are performed in parallel. | 15 days | Please inquire |
| Chemokine Panel | Panel of Human Chemokine GPCR cell based assays that can be used to measure specificity or selectivity during Hit to Lead or Lead Optimization stages of drug development. | 38 Assays (agonist or antagonist mode) | Panel offered to measure agonist or antagonist activity at 1 concentration in duplicate | 20 days | Please inquire |
Table 1: Overview of all Eurofins Discovery GPCR Services.
These GPCR services provide your ultimate flexibility to choose the ideal screening platform to meet your project needs. Whether your focus is hit identification, selectivity profiling, lead optimization, or mechanism of action (MoA), these services can reduce the time and cost of GPCR drug discovery.
