Obesity and Diabetes Assay Product Solutions

Eurofins DiscoverX assays are designed for simplicity and efficiency, enabling reliable results with minimal hands-on time. The workflow follows a straightforward sequence — cells are thawed and plated, compounds are added, and the signal is detected – making it easy to generate robust, reproducible data without the need for complex preparation steps.
 

Our best-in-class target-based assays have been validated, published in numerous peer-reviewed publications, and used extensively in discovery programs for identification and validation, assay development, screening, hit validation, selectivity profiling, and lead optimization.

Industry-leading turnaround times that meet your timelines

Reliable quality control for reproducible results

Flexible partnership and custom assay development to meet your needs

Experience in a variety of highly regulated industries and environments

1. Which is the preferred assay for testing GPCR-based obesity or diabetes therapeutics in potency and lot-release applications?
   Regulatory guidelines, such as those from the FDA (US Food and Drug Administration) and EMEA (European Medicines Evaluation Agency), emphasize the importance of potency assays that adequately measure the relevant mechanism of action (MOA) of drug therapeutics. For various peptide therapeutics directed at the three key GPCR targets (GLP-1, GIP, and glucagon (GCG) receptors), this typically involves demonstrating the ability to stimulate cAMP production in a manner consistent with their intended pharmacological effects on insulin secretion and glucose metabolism.
   
   Measuring cAMP production is a classical method to assess GPCR receptor activity since it reflects the activation of the Gαs-mediated signaling pathway downstream of the receptor and provides a direct and quantitative readout of receptor-mediated signaling. This measurement can be used to compare the potency of different agonists such as semaglutide, tirzepatide, liraglutide, etc.
   
   Eurofins DiscoverX offers MOA-reflective, thaw-and-use cAMP Hunter bioassays that are phase-appropriate for potency testing for GLP-1R and GIPR activation and are rigorously qualified with innovator drugs such as semaglutide, tirzepatide, and retatrutide to establish fit-for-purpose assays for potency and stability testing studies.
   
   
2. How do β-arrestin recruitment and receptor internalization assays contribute to establishing pharmacological profiles for biased agonists targeting the GLP-1, GIP, and glucagon receptors?
   The use of dual and triple agonists to initiate synergistic effects in treating obesity and other metabolic diseases is an emerging area of interest. To establish accurate pharmacology for these therapeutics, the three key GPCR readouts – cAMP, β-arrestin, and receptor internalization – are evaluated.
   
   Quantifying β-arrestin activity (recruitment) in response to GPCR activation is a stoichiometric, sustained, and non-amplified readout that closely reflects the in vivo response to receptor activation, while internalization assays track receptor activation and recycling. This dual analysis is instrumental in optimizing multi-agonist therapies, such as achieving the right balance between GLP-1R and GIPR activity to maximize therapeutic effects and minimize side effects.
   
   An example is tirzepatide, recently approved by the FDA that acts as a biased dual agonist, favoring GIPR over GLP-1R activity. The therapeutic exhibits a pronounced cAMP signaling bias over β-arrestin recruitment at the GLP-1R, thereby reducing GLP-1R internalization.
   
   
3. How does overexpression of the GLP-1 receptor impact the potency of the cAMP readout?
   Overexpression of the GLP-1 receptor can impact the potency of the cAMP readout. When GLP-1 receptors are overexpressed, the increased receptor density can enhance the sensitivity of the cAMP signaling pathway. This often results in a lower EC₅₀ value, indicating a higher apparent potency of agonists. However, this effect may not accurately reflect the in vivo pharmacological activity, as it is an amplified read-out.
   
   To address this, using a doxycycline-inducible GLP-1R cell line, stimulation with defined concentrations of doxycycline results in reproducible differences in receptor expression – correlating with low, medium, and high receptor densities – providing a more accurate estimation of cAMP EC₅₀. This approach allows for the assessment of agonist potency across different receptor densities, offering a clearer understanding of how receptor expression levels influence signaling. By utilizing these inducible cell lines, researchers can better interpret potency data and ensure that it is relevant and translatable to physiological conditions.

View more Frequently Asked Questions for about Eurofins DiscoverX’s bioassays vs cell lines, Cell Banking Program (including long term support for bioassays), custom method development and qualification services, assay transfer support to CRO/CDMO sites, and more.

Eurofins DiscoverX works with global pharmaceutical and biotechnology companies as well as government and academic institutions to support their drug discovery and development programs. The content on this webpage discusses drug compounds in the context of research, assay development, and validation that enable pharmaceutical research. We do not prescribe medications, accept patients, or provide addiction or medical treatment products or services of any kind. Our organization provides products and services supporting scientific and pharmaceutical drug discovery and development for research use only.