EconPapers    
Economics at your fingertips  
 

GzESTY as an optimized cell-based assay for initial steps in GPCR deorphanization

Luca Franchini, Joseph J. Porter, John D. Lueck and Cesare Orlandi ()
Additional contact information
Luca Franchini: University of Rochester Medical Center
Joseph J. Porter: University of Rochester Medical Center
John D. Lueck: University of Rochester Medical Center
Cesare Orlandi: University of Rochester Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract G protein-coupled receptors (GPCRs) are key pharmacological targets, yet many remain underutilized due to unknown activation mechanisms and ligands. Orphan GPCRs, lacking identified natural ligands, are a high priority for research, as identifying their ligands will aid in understanding their functions and potential as drug targets. Most GPCRs, including orphans, couple to Gi/o/z family members, however current assays to detect their activation are limited, hindering ligand identification efforts. We introduce GzESTY, a sensitive, cell-based assay developed in an easily deliverable format designed to study the pharmacology of Gi/o/z-coupled GPCRs and assist in deorphanization. We optimized assay conditions and developed an all-in-one vector employing cloning methods to ensure the correct expression ratio of GzESTY components. GzESTY successfully assessed activation of a library of ligand-activated GPCRs, detecting both full and partial agonism, and responses from endogenous GPCRs. Notably, with GzESTY we established the presence of endogenous ligands for GPR176 and GPR37 in brain extracts, validating its use in deorphanization efforts. This assay enhances the ability to find ligands for orphan GPCRs, expanding the toolkit for GPCR pharmacologists.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59850-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59850-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59850-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().

 
Page updated 2025-05-17
Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59850-8