182498-32-4 Usage
Description
SB 225002 is a selective non-peptide inhibitor of CXCR2, a seven-transmembrane G protein-coupled receptor involved in various inflammatory processes. It effectively inhibits the binding of IL-8 to CXCR2, demonstrating potent and selective antagonism with an IC50 value of 22 nM.
Uses
Used in Pharmaceutical Industry:
SB 225002 is used as a potent and selective CXCR2 antagonist for the inhibition of IL-8 binding to CXCR2, which plays a crucial role in various inflammatory processes. Its ability to inhibit neutrophil chemotaxis in response to IL-8 in vitro and block neutrophil margination induced by IL-8 in vivo makes it a valuable compound for the development of anti-inflammatory drugs.
Used in Research Applications:
SB 225002 is used as a research tool for studying the role of CXCR2 in various inflammatory conditions. Its high selectivity and potency make it an ideal compound for investigating the mechanisms of action and potential therapeutic targets related to CXCR2-mediated inflammation.
Used in Drug Discovery:
SB 225002 is used as a lead compound in the development of new drugs targeting CXCR2-mediated inflammatory pathways. Its ability to reduce neutrophil influx, the production of inflammatory mediators, and tissue damage in TNBS-induced colitis in mice highlights its potential as a therapeutic agent for treating inflammatory disorders.
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) 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
Check Digit Verification of cas no
The CAS Registry Mumber 182498-32-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,2,4,9 and 8 respectively; the second part has 2 digits, 3 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 182498-32:
(8*1)+(7*8)+(6*2)+(5*4)+(4*9)+(3*8)+(2*3)+(1*2)=164
164 % 10 = 4
So 182498-32-4 is a valid CAS Registry Number.
InChI:InChI=1/C13H10BrN3O4/c14-9-3-1-2-4-10(9)15-13(19)16-11-6-5-8(17(20)21)7-12(11)18/h1-7,18H,(H2,15,16,19)
182498-32-4Relevant articles and documents
Structural optimization of a CXCR2-directed antagonist that indirectly inhibits γ-secretase and reduces Aβ
Bakshi, Pancham,Jin, Chao,Broutin, Pierre,Berhane, Beniam,Reed, Jon,Mullan, Michael
experimental part, p. 8102 - 8112 (2010/03/24)
Amyloid β (Aβ), a key molecule in the pathogenesis of Alzheimer's disease (AD), is derived from the amyloid precursor protein (APP) by sequential proteolysis via β- and γ-secretases. Because of their role in generation of Aβ, these enzymes have emerged as important therapeutic targets for AD. In the case of γ-secretase, progress has been made towards designing potent inhibitors with suitable pharmacological profiles. Direct γ-secretase inhibitors are being evaluated in clinical trials and new strategies are being explored to block γ-secretase activity indirectly as well. In this regard, we have previously reported an indirect regulation of γ-secretase through antagonism of CXCR2, a G-protein coupled receptor (GPCR). We demonstrated that N-(2-hydroxy-4-nitrophenyl)-N′-(2-bromophenyl)urea (SB225002), a selective inhibitor of CXCR2 also plays a role in an indirect inhibition of γ-secretase. Furthermore, we reported a ～5-fold difference in the selective inhibition of APP versus Notch processing via γ-secretase following treatment with SB225002. Herein we describe the synthesis and optimization of SB225002. By determination of the structure-activity relationship (SAR), we derived small molecules that inhibit Aβ40 production with IC50 values in the sub-micromolar range in a cell-based assay and also validated the potential of CXCR2 as a new target for therapeutic intervention in AD.
IL-8 RECEPTOR ANTAGONISTS
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, (2008/06/13)
This invention relates to the novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
