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Webinar: Unlocking Orphan GPCRs with an Innovative Forward Trafficking Approach


Join this live webinar to learn about orphan GPCRs as drug targets and the challenges related to lead identification.

Speaker: Dr Layton Smith

February 23, 2022

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G protein-coupled receptors (GPCRs) are seven transmembrane receptors capable of transducing a wide variety of extracellular stimuli such as light, taste and smell, into intracellular signals mediated by G-proteins, β-arrestins and other effectors. As a result of their broad signaling capabilities and subsequent mediation of physiological functions, they are the targets for more than one-third of currently prescribed therapeutics.


Despite being the most fruitful target class for drug discovery, many GPCRs remain under-exploited from both a basic science and drug discovery perspective. Approximately one-third of the 350 non-olfactory GPCRs in the human genome are orphan receptors whose endogenous ligands are unknown and many more have been inadequately characterized. Thus, much of the druggable space in the GPCR superfamily remains an untapped resource of potential therapeutic targets.


To address this gap, we have initiated a systematic approach to the identification of chemical probes of orphan GPCRs using a recently developed platform called the Ligand-Induced Forward Trafficking (LIFT) assay. With this assay and a highly curated library of compounds and new approaches to determine compound-target engagement, we identified a series of probe compounds for GPR20, an orphan receptor.


During this webinar, assay development, high-throughput screening (HTS) and hit confirmation and validation as well as the incorporation of Eurofins DiscoverX’s Enzyme Fragment Complementation technology will be discussed. Hit-to-lead efforts produced a potent and highly selective probe compound that, when applied to native human cellular models, revealed a heretofore unappreciated role for GPR20 in the function of interstitial cells of Cajal.