SB-225002
货号：
IS2010
品牌：
Jinpan
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产品简介
| 有效期 | 2年 |
| MDL | MFCD00078305 |
| 别名 | 1-(2-溴苯基)-3-(2-羟基-4-硝基苯基)脲 |
| 英文名称 | SB-225002 |
| CAS | 182498-32-4 |
| 分子式 | C13H10BrN3O4 |
| 分子量 | 352.14 |
| 储存条件 | RT |
| 纯度 | ≥98% |
| 外观（性状） | White to beige Powder |
| 单位 | 瓶 |
| 生物活性 | SB225002 是一种有效的选择性 CXCR2 拮抗剂，IC50 为 22 nM。[1-5] |
| In Vitro | SB225002（SB 225002）是125 I-IL-8与CXCR2结合的拮抗剂，IC 50 = 22 nM。 SB225002显示出比CXCR1和其他四种测试的7-TMR高150倍的选择性。 SB225002是一种有效的兔CXCR2拮抗剂，可抑制兔PMN趋化性，以响应人IL-8或GROα的最佳浓度（IC50值分别为30和70 nM。在这些细胞中（PMN，HL60，CXCR1-RBL-2H3） SB225002对IL-8和GROα介导的钙动员产生浓度依赖性抑制，IC50值分别为8和10 nM。在稳定转染CXCR2的3ASASE细胞中，SB 225002剂量依赖性地抑制两者诱导的钙动员。 GROα和IL-8，IC50值分别为20和40 nM [1]。用SB225002处理的WHCO1细胞表现出40％的细胞增殖减少。用400 nM SB225002（SB 225002）阻断WHCO1细胞中的CXCR2信号传导显著降低细胞增殖约40％至50％[2]。 |
| In Vivo | SB225002（SB 225002）选择性地阻断兔中IL-8诱导的中性粒细胞边缘化[1]。使用选择性拮抗剂SB225002（2mg / kg）或中和CXCR2抗血清阻断CXCR2。在正常饮食中，CXCR2拮抗剂SB225002降低西方饮食和野生型小鼠ApoE – / – 小鼠缺血半球的中性粒细胞计数[3]。 SB225002显著减弱小胶质细胞激活和BBB损伤，增加髓鞘形成，并减少LPS致敏HI后白质中的星形胶质细胞增生[4]。 |
| 激酶实验 | CHO-CXCR1 and CHO-CXCR2 membranes are prepared. Assays are performed in 96-well microtiter plates where the reaction mixture contained 1.0 μg/mL membrane protein in 20 mM Bis-Tris-propane, pH 8.0, with 1.2 mM MgSO4, 0.1 mM EDTA, 25 mM NaCl, and 0.03% CHAPS and SB 225002 (10 mM stock in Me2SO) added at the indicated concentrations, the final Me2SO concentration is <1% under standard binding conditions. Binding is initiated by addition of 0.25 nM 125I-IL-8 (2,200 Ci/mmol). After 1-h incubation at room temperature the plate is harvested using a Tomtec 96-well harvester onto a glass fiber filtermat blocked with 1% polyethyleneimine, 0.5% BSA and washed three times with 25 mM NaCl, 10 mM Tris?HCl, 1 mM MgSO4, 0.5 mMEDTA, 0.03% CHAPS, pH 7.4. The filter is dried, sealed in a sample bag containing 10 mL of Wallac 205 Betaplate liquid scintillation fluid, and counted with a Wallac 1205 Betaplate liquid scintillation counter[1]. |
| SMILES | O=C(NC1=CC=C([N+]([O-])=O)C=C1O)NC2=CC=CC=C2Br |
| 靶点 | CXCR |
| 动物实验 | Mice[3]Male 7-8 weeks old wildtype (C57BL/6J, Harlan) and ApoE?/? mice, which are generated on the same C57BL/6 background, are either fed with a normal chow or a cholesterol rich chow for 6 weeks and submitted to 20 min of left-sided middle cerebral artery occlusion (MCAO) or sham surgery. Animals are randomly attributed to treatment paradigms, and experimenters are blinded at all stages of interventions and data analysis. The selective CXCR2 antagonist SB225002 (2 mg/kg) or vehicle (1% DMSO in PBS) is injected intraperitoneally (i.p.) at 0, 24 and 48 hours post-ischemia. In other experiments, CXCR2 is specifically blocked by i.p. injection of a neutralizing rabbit anti-CXCR2 serum (300 μL) at 0 hours, 24 hours and 48 hours post-ischemia. In the latter studies, normal rabbit serum (NRS) served as control. In some experiments, neutrophils are depleted by i.p. injection of 200 μg anti-mouse Ly6G 24 hours before and 24 hours after ischemia. In these experiments, 200 μg of an isotype control antibody is delivered as control. Rats[4]In this study, 10-12 Sprague-Dawley rat pups per dam are used. The pups receive intraperitoneal injections of SB225002 (1 or 3 mg/kg, diluted in NS containing 0.33 % Tween 80) or vehicle (NS solution containing 0.33 % Tween 80) 30 min before lipopolysaccharide (LPS) administration and immediately after hypoxic ischemia (HI). The pups are randomly assigned to four groups: control (pups unexposed to LPS or HI, N=14), vehicle (NS injections 30 min before LPS administration and immediately after HI, N=18), and SB-1 (1 mg/kg, N=14) and SB-3 (3 mg/kg, N=18) (SB225002 injections 30 min before LPS administration and immediately after HI). |
| 细胞实验 | Three esophageal squamous cell carcinoma cell lines WHCO1, WHCO5, and WHCO6 originally established from surgical biopsies of primary esophageal squamous cell carcinomas are cultured in DMEM containing 10% FCS at 37°C in a humidified atmosphere of 5% CO2. MTT assays are carried out using the Cell Proliferation kit. Briefly, 1.5×103 cells are plated in 96-well plates in a final volume of 180 μL DMEM per well. SB 225002 (400 nM) is added to cells and 0.001% DMSO (solvent) is added as a control. After the indicated incubation period, 18 μL of the MTT labeling reagent (final concentration 0.5 mg/mL) is added to each well and incubated for 4 hours in a humidified atmosphere. One hundred eighty microliters of the solubilization solution are added to each well and the plates are left overnight at 37°C. The spectrophotometric absorbance of samples is measured at 595 nm using a microtiter plate reader[2]. |
| 数据来源文献 | [1]. White JR, et al. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem. 1998 Apr 24;273(17):10095-8. [2]. Wang B, et al. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006 Mar 15;66(6):3071-7. [3]. Herz J, et al. Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice. Stroke. 2015 Oct;46(10):2916-25. [4]. Wang LY, et al. CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain. J Neuroinflammation. 2016 Jan 6;13:6. [5]. Shi ZR, et al. Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis. J Autoimmun. 2018 May;89:30-40. |
| 规格 | 5mg 10mg |
是一种有效的选择性 CXCR2 非肽拮抗剂。