GPCR Assay Services

Go from hit to lead faster with compound profiling assays that capture GPCR signaling dynamics in living cells. Our unique biosensor-based discovery platform quantifies multiple signaling parameters in real time to enable decisions based on clinically-relevant data. Our fast turnaround time helps reduce the time to the clinic. We will perform experiments to advance your projects and programs, for example by optimizing assays, profiling compounds, exploring mechanisms and kinetically characterizing signaling dynamics.

Schedule a meeting with our GPCR discovery team.

Compound Profiling

Measure Gs, Gi, Gq, and β-arrestin activity in real time.
Quantify the dynamics of signaling, including signaling duration, initial rate, and desensitization kinetics.
Dose-response curves from initial rate, peak activation, and signal plateau.
Quantify partial or biased agonism.
Estimate efficacy, potency and desensitization rate.

Case study: Profiling µ-opioid receptor agonists in living cells
with biosensors for cAMP and β-arrestin.

Time course data from cAMP cADDis assay fit to kinetic equations. Analysis estimates initial rate of signaling (dashed line) at each dose of morphine at the µ-opioid receptor.

cADDis biosensor reveals distinct temporal profiles of cAMP signaling.

CRCs for 5 µ-opioid receptor agonists using the initial rate of activation.

Summary of results at the µ-opioid receptor

All compounds generate cAMP at a similar rate, except buprenorphine (a partial agonist).
Small molecules recruit arrestin more slowly than peptides.
The ratio of initial rates can be used to quantify bias for cAMP over arrestin – small molecules are biased for cAMP.

Video: Description of our Assay Services

Data Analysis

Time course equations for a variety of curve shapes entered into GraphPad Prism as a plug-in.

Parameters include:

- Initial rate of signal generation
- Fade (desensitization) rate
- Steady-State signal level
- Peak level and peak time

References

Rise and fall to steady-state curve

Rise to steady-state curve

Quantifying GPCR Signaling and Desensitization Kinetics

Waveform data fitted to equations to quantify:

- Signal generation rate
- Desensitization rate
- Signal clearance rate
- Differences between GPCRs in signaling mechanisms and rates

Assay Optimization Services

Our GPCR Discovery Team can kick start your in-house discovery efforts with our assay optimization services. You will receive your receptor in a BacMam delivery vector to ensure consistent, controllable receptor expression, an optimized protocol, and biosensor assay starter kit. Choose from GPCR assays for β-arrestin, cAMP, DAG, PIP₂, and Calcium, or ask us about our biosensors for cGMP, Cell Stress, and SARS-CoV-2 protease inhibitors.