SB 225002

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 IC₅₀ value of 22 nM. SB225002 inhibits neutrophil chemotaxis in response to IL-8 in vitro (IC₅₀ = 20 nM) and blocks neutrophil margination induced by IL-8 in vivo (IC₅₀ = 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.

storage

Store at RT

References

1) White et al. (1998), Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration; J. Biol. Chem. 273 10095 2) Du et al. (2013) SB225002 Promotes Mitotic Catastrophe in Chemo-Sensitive and -Resistant Ovarian Cancer Cells Independent of p53 Status In Vitro; PLoS One. 8 e54572 3) Shen et al. (2013), Interleukin-8 prevents oxidative stress-induced human endothelial cell senescence via telomerase activation; Int. Immunopharmacol. 16 261 4) Lane et al. (2001), Interleukin-8 Stimulates Human Immunodeficiency Virus Type 1 Replication and Is a Potential New target for Antiretroviral Therapy; J. Virol. 75 8195 5) Wu et al. (2015), CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation; J. Neuroinflammation 12 98