ArticleBritish journal of pharmacology2012
Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2 non-competitive allosteric inhibitor.
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 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Recurrent urinary tract infection genetic risk: a systematic review and gene network analysis.International urogynecology journal · 2024Pooled it
- Trial
- Ladarixin, an inhibitor of the interleukin-8 receptors CXCR1 and CXCR2, in new-onset type 1 diabetes: A multicentre, randomized, double-blind, placebo-controlled trial.Diabetes, obesity & metabolism · 2022Trial
- Multi-population genome-wide association meta-analysis of acute and chronic pancreatitis.medRxiv : the preprint server for health sciences · 2026Article
- Functional and Transcriptional Responses of Neutrophils from Dogs Living Under Different Housing Conditions Following In Vitro Lipopolysaccharide Stimulation.International journal of molecular sciences · 2026Article
- The dual non-competitive CXCR1/2 inhibitor ladarixin impairs neutrophil extravasation without altering intravascular adhesion.Haematologica · 2026Article
- CXCL8 greatly enhances neutrophil extracellular traps formation induced by calcium crystalsFrontiers in pharmacology · 2026Article
- Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat.Diabetes & metabolism journal · 2025Article
- Targeting CXCR2 signaling in inflammatory lung diseases: neutrophil-driven inflammation and emerging therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Review
- The CXCL8/MAPK/hnRNP-K axis enables susceptibility to infection by EV-D68, rhinovirus, and influenza virus in vitro.Nature communications · 2025Article
- Comprehensive profiling of chemokine and NETosis-associated genes in sarcopenia: construction of a machine learning-based diagnostic nomogram.Frontiers in medicine · 2025Article
- Recent advances in the genetics and innate immune cells of bullous pemphigoid.Frontiers in immunology · 2025Review
- Review
- Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation.Journal of diabetes research · 2024Review
- Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches.Clinical reviews in allergy & immunology · 2023Review
- Identification of key biomarkers in RF-negative polyarticular and oligoarticular juvenile idiopathic arthritis by bioinformatic analysis.Pediatric rheumatology online journal · 2023Article
- Therapeutic inhibition of CXCR1/2: where do we stand?Internal and emergency medicine · 2023Review
- Identification of a Salt Bridge That Is Functionally Important for Chemokine Receptor CXCR1 but not CXCR2.ACS pharmacology & translational science · 2023Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeDF 2156A is a new dual inhibitor of IL-8 receptors CXCR1 and CXCR2 with an optimal pharmacokinetic profile. We characterized its binding mode, molecular mechanism of action and selectivity, and evaluated its therapeutic potential. EXPERIMENTAL APPROACH: The binding mode, molecular mechanism of action and selectivity were investigated using chemotaxis of L1.2 transfectants and human leucocytes, in addition to radioligand and [(35) S]-GTPγS binding approaches. The therapeutic potential of DF 2156A was evaluated in acute (liver ischaemia and reperfusion) and chronic (sponge-induced angiogenesis) experimental models of inflammation. KEY
resultsA network of polar interactions stabilized by a direct ionic bond between DF 2156A and Lys(99) on CXCR1 and the non-conserved residue Asp(293) on CXCR2 are the key determinants of DF 2156A binding. DF 2156A acted as a non-competitive allosteric inhibitor blocking the signal transduction leading to chemotaxis without altering the binding affinity of natural ligands. DF 2156A effectively and selectively inhibited CXCR1/CXCR2-mediated chemotaxis of L1.2 transfectants and leucocytes. In a murine model of sponge-induced angiogenesis, DF 2156A reduced leucocyte influx, TNF-α production and neovessel formation. In vitro, DF 2156A prevented proliferation, migration and capillary-like organization of HUVECs in response to human IL-8. In a rat model of liver ischaemia and reperfusion (I/R) injury, DF 2156A decreased PMN and monocyte-macrophage infiltration and associated hepatocellular injury. CONCLUSION AND IMPLICATIONS: DF 2156A is a non-competitive allosteric inhibitor of both IL-8 receptors CXCR1 and CXCR2. It prevented experimental angiogenesis and hepatic I/R injury in vivo and, therefore, has therapeutic potential for acute and chronic inflammatory diseases.
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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.