ArticleBritish journal of pharmacology2012
Pharmacological characterization of a small-molecule agonist for the chemokine receptor CXCR3.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Structural visualization of small molecule recognition by CXCR3 uncovers dual-agonism in the CXCR3-CXCR7 system.Nature communications · 2025Article
- Multiplex Detection of Fluorescent Chemokine Binding to CXC Chemokine Receptors by NanoBRET.International journal of molecular sciences · 2024Article
- Structural insights into the activation and inhibition of CXC chemokine receptor 3.Nature structural & molecular biology · 2024Article
- GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization.Science signaling · 2024Article
- Development of tolerance to chemokine receptor antagonists: current paradigms and the need for further investigation.Frontiers in immunology · 2023Review
- New pairings and deorphanization among the atypical chemokine receptor family - physiological and clinical relevance.Frontiers in immunology · 2023Review
- Germinal Center-Related G Protein-Coupled Receptors in Antibody-Mediated Autoimmune Skin Diseases: from Basic Research to Clinical Trials.Clinical reviews in allergy & immunology · 2022Review
- Biased agonists of the chemokine receptor CXCR3 differentially signal through GαScience signaling · 2022Article
- Article
- The Synthetic Dipeptide Pidotimod Shows a Chemokine-Like Activity through CXC Chemokine Receptor 3 (CXCR3).International journal of molecular sciences · 2019Article
- Review
- Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1.International journal of molecular sciences · 2019Article
- Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1.The Journal of biological chemistry · 2019Article
- Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization.International journal of molecular sciences · 2018Review
- Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation.Science signaling · 2018Article
- Structural Analysis of Chemokine Receptor-Ligand Interactions.Journal of medicinal chemistry · 2017Review
- Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands.Frontiers in immunology · 2017Review
- The Viral G Protein-Coupled Receptor ORF74 Hijacks β-Arrestins for Endocytic Trafficking in Response to Human Chemokines.PloS one · 2015Article
- Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study.PloS one · 2015Article
- Regulation of G protein-coupled receptors by allosteric ligands.ACS chemical neuroscience · 2013Review
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe chemokine receptor CXCR3 is a GPCR found predominantly on activated T cells. CXCR3 is activated by three endogenous peptides; CXCL9, CXCL10 and CXCL11. Recently, a small-molecule agonist, VUF10661, has been reported in the literature and synthesized in our laboratory. The aim of the present study was to provide a detailed pharmacological characterization of VUF10661 by comparing its effects with those of CXCL11. EXPERIMENTAL APPROACH: Agonistic properties of VUF10661 were assessed in a chemotaxis assay with murine L1.2 cells transiently transfected with cDNA encoding the human CXCR3 receptor and in binding studies, with [(125)I]-CXCL10 and [(125)I]-CXCL11, on membrane preparations from HEK293 cells stably expressing CXCR3. [(35)S]-GTPγS binding was used to determine its potency to induce CXCR3-mediated G protein activation and BRET-based assays to investigate its effects on intracellular cAMP levels and β-arrestin recruitment. KEY
resultsVUF10661 acted as a partial agonist in CXCR3-mediated chemotaxis, bound to CXCR3 in an allosteric fashion in ligand binding assays and activated G(i) proteins with the same efficacy as CXCL11 in the [(35)S]-GTPγS binding and cAMP assay, while it recruited more β-arrestin1 and β-arrestin2 to CXCR3 receptors than the chemokine. CONCLUSIONS AND IMPLICATIONS: VUF10661, like CXCL11, activates both G protein-dependent and -independent signalling via the CXCR3 receptor, but probably exerts its effects from an allosteric binding site that is different from that for CXCL11. It could stabilize different receptor and/or β-arrestin conformations leading to differences in functional output. Such ligand-biased signalling might offer interesting options for the therapeutic use of CXCR3 agonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.