Description
CXCR2 (IL-
8RB) is a seven-
transmembrane G protein-
coupled receptor whose physiological ligands include IL-
8 (CXCL8) and growth related oncogene α (Gro-
α; CXCL1). IL-
8 and Gro-
α are pro-
inflammatory CXC chemokines that act as chemoattractants, especially for neutrophils, and promote angiogenesis. SB 225002 is a selective non-
peptide inhibitor of CXCR2, inhibiting IL-
8 binding to CXCR2 with an IC
50 value of 22 nM. SB225002 inhibits neutrophil chemotaxis in response to IL-
8
in vitro (IC
50 = 20 nM) and blocks neutrophil margination induced by IL-
8
in vivo (IC
50 = 30 nM). Similarly, SB 225002 reduces neutrophil influx, the production of inflammatory mediators, and tissue damage in TNBS-
induced colitis in mice.
Uses
SB 225002 is a potent and selective CXCR2 antagonist with the ability to inhibit interleukin IL-8 binding to CXCR2.
Definition
ChEBI: 1-(2-bromophenyl)-3-(2-hydroxy-4-nitrophenyl)urea is a nitrophenol.
Biological Activity
Potent and selective CXCR2 chemokine receptor antagonist (IC 50 = 22 nM) that displays > 150-fold selectivity over CXCR1 receptors. Causes inhibition of IL-8 and GRO α -mediated calcium mobilization in HL60 cells (IC 50 values are 8 and 10 nM respectively). Prevents IL-8-induced neutrophil chemotaxis in vitro and sequestration in vivo . Inhibits HIV replication in lymphocytes and macrophages.
Biochem/physiol Actions
SB-225002 is a potent nonpeptide inhibitor of chemokine receptor CXCR2 with an IC50 of 22 nM for inhibiting interleukin IL-8 binding to CXCR2 and > 150-fold selectivity over CXCR1 receptors. CXCR2 binds many different immune cell chemoattractants. SB-225002 is crucial for cancer progression and is involved in inflammatory diseases like COPD, rheumatoid arthritis, and ulcerative colitis.
References
[1] J R WHITE. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration.[J]. The Journal of Biological Chemistry, 1998, 273 17: 10095-10098. DOI:
10.1074/jbc.273.17.10095[2] MEIRONG DU. SB225002 promotes mitotic catastrophe in chemo-sensitive and -resistant ovarian cancer cells independent of p53 status in vitro.[J]. PLoS ONE, 2013: e54572. DOI:
10.1371/journal.pone.0054572[3] XIAO-HUA SHEN . Interleukin-8 prevents oxidative stress-induced human endothelial cell senescence via telomerase activation[J]. International immunopharmacology, 2013, 16 2: Pages 261-267. DOI:
10.1016/j.intimp.2013.04.003[4] B. LANE. Interleukin-8 Stimulates Human Immunodeficiency Virus Type 1 Replication and Is a Potential New Target for Antiretroviral Therapy[J]. Journal of Virology, 2001, 75 1: 8195-8202. DOI:
10.1128/jvi.75.17.8195-8202.2001[5] FENGJIAO WU. CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation.[J]. Journal of Neuroinflammation, 2015: 98. DOI:
10.1186/s12974-015-0316-6
