CXCR1
CXCR1 is a CXCL8/IL-8-responsive G protein-coupled chemokine receptor that mediates neutrophil recruitment and cytotoxic activity at inflammatory or infectious sites[1]. Mechanistically, CXCL8 activates CXCR1 and CXCR2, but CXCL8 monomers and dimers differentially regulate receptor phosphorylation, desensitization, β-arrestin translocation, internalization, and ERK signaling[1]. Structural studies show CXCR1 complexed with CXCL8 and Gαi, and, compared with related isoforms, CXCR1 strongly prefers monomeric CXCL8, whereas dimeric CXCL8 creates steric clashes with extracellular loop 2[2]. In tumor models, CXCR1 and CXCR2 agonists produced by tumors induce neutrophil extracellular traps that interfere with CD8+ T-cell and NK-cell cytotoxicity[3]. For experimental applications, repertaxin/reparixin functions as a non-competitive allosteric blocker of CXCR1/CXCR2, preventing CXCL8 receptor signaling, PMN chemotaxis, adhesion, CD11b up-regulation, granule release, and cytokine production[4][5].
References:
- [1]. Nasser MW, et al. Differential activation and regulation of CXCR1 and CXCR2 by CXCL8 monomer and dimer. J Immunol. 2009 Sep 1;183(5):3425-32. [Content Brief]
- [2]. Ishimoto N, et al. Structural basis of CXC chemokine receptor 1 ligand binding and activation. Nat Commun. 2023 Jul 11;14(1):4107. [Content Brief]
- [3]. Teijeira Á, et al. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity. Immunity. 2020 May 19;52(5):856-871.e8. [Content Brief]
- [4]. Bertini R, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6. [Content Brief]
- [5]. Casilli F, et al. Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2. Biochem Pharmacol. 2005 Feb 1;69(3):385-94. [Content Brief]
All Product Categories
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CXCR1 Related Products (11)
Related Products (11)
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Reparixin L-lysine salt
0 ImagesSynonyms: Repertaxin L-lysine saltReparixin L-lysine salt is an allosteric inhibitor of chemokine receptor 1/2 (CXCR1/2) activation.
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SX-517
0 ImagesSX-517 is a dual CXCR2/1 antagonist, containing boronic acid. SX-517 inhibits CXCL1-induced Ca2+ flux (IC50=38 nM), and antagonizes CXCL8-induced [(35)S]GTPγS binding (IC50=60 nM) and ERK1/2 phosphorylation. SX-517 has significant ability for inflammation suppression, in both humanized polymorphonuclear (PMN) cells and in murine model.
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Ladarixin sodium
0 ImagesSynonyms: DF 2156A
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SCH-900875
0 ImagesSCH-900875 is an orally active, brain-penetrant and selective CXCR3 receptor inhibitor, which also shows high selectivity over CXCR1 and CXCR2 receptors. SCH-900875 binds to CXCR3, blocking the binding of ligands CXCL9, CXCL10, and CXCL11, inhibiting downstream G protein and β-arrestin signaling pathways to suppress inflammatory cell migration. SCH-900875 is promising for research of autoimmune diseases (rheumatoid arthritis, multiple sclerosis) and inflammatory disorders (psoriasis, inflammatory bowel disease).
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CXCR2-IN-2
0 ImagesCXCR2-IN-2 is a selective, brain penetrant, and orally bioavailable CXCR2 antagonist (IC50=5.2 nM/1 nM in β-arrestin assay/CXCR2 Tango assay, respectively). CXCR2-IN-2 displays ~730-fold selectivity over CXCR1 and >1900-fold selectivity over all other chemokine receptors. CXCR2-IN-2 inhibits human whole blood Gro-α induced CD11b expression with an IC50 of 0.04 μM.
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PMX464
0 ImagesCat. No.: HY-108534CAS No.: 485842-97-5Synonyms: AW 464PMX464 (AW 464) is a thiol-reactive quinol compound and an inhibitor of the thioredoxin-thioredoxin reductase (Trx/TrxR) system, with an IC50 value of 6.5 μM against TrxR. PMX464 acts by irreversibly inhibiting the thioredoxin (Trx-1) system, blocking HIF-1α transcriptional activation and the NF-κB inflammatory pathway, inducing apoptosis, attenuating platelet function and inhibiting thrombosis, and specifically disrupting the trypanothione antioxidant metabolic network in parasites. PMX464 is used in research concerning malignant tumors (colorectal cancer, breast cancer, renal cancer, and leukemia), pulmonary inflammation, African sleeping sickness, and antithrombotic applications.
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BC-1485
0 ImagesCat. No.: HY-114366CAS No.: 2035085-19-7BC-1485 is a small molecule inhibitor of Fibrosis-inducing E3 ligase 1 (FIEL1). BC-1485 protects PIAS4 from ubiquitin-mediated degradation. BC-1485 decreases α-SMA, BAL and CXCL1. BC-1485 ameliorates fibrotic lung injury in murine models.
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