The value of GPCR cell-based assays in drug discovery

18 September 2024


Join this webinar to discover how GPCR functional, cell-based assays determine off-target effects, reveal safety issues, and define drug mechanism of action to ultimately evaluate the therapeutic potential of candidate molecules.

In the candidate lead optimisation phase of drug discovery for G Protein-Coupled Receptor (GPCR) ligands, it is well established that functional cell-based assays are valuable for determining off-target effects and safety issues. These assays can be used to fully characterise candidate molecules, including determining drug mechanism of action and therapeutic value.

GPCRs can be likened to nature’s Swiss Army Knife, equipped to manipulate a multitude of cellular functions. Studies on second messenger signalling (via cAMP, IP3, and calcium) and β-arrestin recruitment, unravel a complex array of receptor-based cellular signals that are usually biased across various signalling pathways. GPCRs’ internalisation to cellular locations for further signalling (ie, endoplasmic reticulum signalling) make them functionally diverse and may be exploited therapeutically. The allosteric nature of GPCRs causes ligand-specific effects (ie, biased signalling, location bias), thereby creating many possibilities for unique cellular outcomes. Thus, it is imperative to examine outcomes of candidate ligand and GPCR interactions to fully understand the efficacies of any candidate molecule. The key to this process is through cell-based functional assays.

The exploration of ligand-induced effects with cell-based, functional assays serves a two-fold purpose: to detect unwanted effects of a candidate molecule, and to detect new possible efficacies for further consideration in a chemical scaffold. Current evidence suggests it is best to understand as much as possible about a candidate molecule to evaluate in vivo effects and assess optimal properties in follow-up molecules.

Key learning points

  • Discover key differences in binding versus functional assay formats and the theoretical limitations of animal orthologue assays, especially for allosteric molecules
  • Review how the study of GPCR agonism has changed over the past 50 years into the sophisticated studies presently available that go beyond second messenger measurements to reveal “multiple efficacies” and consider “biased signalling,” a mandatory consideration for all GPCR agonist programmes
  • Learn how cell-based assay “volume control” (testing in systems of varying sensitivity) can reveal complex behaviours of drug candidates
  • Examine case studies highlighting the application of cell-based assay data to understand drug candidate actions that affect clinical profiles (eg, positive allosteric modulator, partial agonists, inverse agonists, biased agonism / antagonism)

Register to join this webinar for free


Terry Kenakin

Terry Kenakin, PhD, Professor of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

Dr Kenakin earned his BS in chemistry and doctorate in Pharmacology at the University of Alberta in Edmonton, Canada, followed by post-doctoral training at University College, London, UK. He has amassed over 30 years of experience in industrial drug discovery (including seven years at Burroughs-Wellcome and 25 years at GlaxoSmithKline) where he was involved in, and led, many drug discovery programmes – including one leading to the AIDS drug Aplaviroc. For the past 14 years, he has served as a Professor of Pharmacology at UNC. His interests range from allosteric protein function to drug receptor pharmacodynamics as applied to new drug discovery.


Is the webinar free?
Yes – there is no charge to watch the webinar, either live or on-demand.

When will the webinar take place?
The webinar will take place live on 18th September at 16:00 BST

I’m busy. Can I watch it later?
The webinar will become available to watch on-demand shortly after the live webinar takes place.

What are the benefits of attending live?
During the live webinar, you’ll be able to ask the speakers your questions, which will then be answered during the live Q&A session towards the end of the webinar.

How long will the webinar be?
This webinar will last for up to one hour.

What do I need to watch this webinar?
All you need is a computer with an internet connection. Be sure to use headphones if in an office environment.

Do I receive a certificate?
Yes, you will receive a certificate if you attend the webinar live. The certificate will be sent with your on-demand video link.