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Updated: May 31, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood
Gebhard Thoma1, Rolf Baenteli, Ian Lewis
1Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, Lichtstrasse 35, CH-4056 Basel, Switzerland.
Abstract:
The structure-activity relationship of highly potent special ergolines which selectively block the chemokine receptor CXCR3 is reported. The most potent compounds showed IC(50) values below 10nM in both ligand binding and Ca(2+)-mobilization assays. However, these compounds were poorly active in an assay that measures receptor occupancy in blood. Introduction of polar substituents led to derivatives with IC(50) values below 10nM in this assay. Among them was compound 11a which showed both a favorable PK profile and cross reactivity with rodent CXCR3 making it a promising tool compound to further explore the role of CXCR3 in animal models.
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