Antileukinate
目录号 : GC42817
A CXCR2 chemokine receptor antagonist
Cas No.:138559-60-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Antileukinate is a synthetic hexapeptide with an acetylated amino terminus and an amidated carboxyl terminus that inhibits the binding of CXC chemokines to the chemokine receptor CXCR2. It inhibits IL-8 binding to neutrophils (Ki = 2.7-13 µM), prevents neutrophil chemotaxis and β-glucuronidase release, and blocks IL-8-induced skin edema in rabbits. At 53 mg/kg, antileukinate has been shown to protect mice against acute pancreatitis and associated lung injury.
| Cas No. | 138559-60-1 | SDF | |
| Canonical SMILES | CC(N[C@H](C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CC1=CNC2=C1C=CC=C2)C(N[C@@H](CC3=CNC4=C3C=CC=C4)C(N[C@H](C(N[C@@H](CCCNC(N)=N)C(N)=O)=O)CS)=O)=O)=O)=O)CCCNC(N)=N)=O | ||
| 分子式 | C45H66N18O7S | 分子量 | 1003.2 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 5 mg/ml,PBS (pH 7.2): 2 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.9968 mL | 4.9841 mL | 9.9681 mL |
| 5 mM | 0.1994 mL | 0.9968 mL | 1.9936 mL |
| 10 mM | 0.0997 mL | 0.4984 mL | 0.9968 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Antileukinate, a hexapeptide inhibitor of CXC-chemokine receptor, suppresses bleomycin-induced acute lung injury in mice
Lung 2002;180(6):339-48.PMID:12647235DOI:10.1007/s00408-002-0106-7.
A hexapeptide, Ac-RRWWCR-NH(2) (Antileukinate), has been reported to be a potent inhibitor of CXC-chemokine receptor. However, the in vivo anti-inflammatory activity of this agent has not been tested except in a rabbit skin edema model. This study was undertaken to investigate the effect of subcutaneously administered Antileukinate on experimental bleomycin-induced acute lung injury in mice, in which CXC-chemokines have been reported to be involved. Lung injury was assessed on the basis of histopathology, the number of total cells, the percentage of neutrophils, and protein concentration in the bronchoalveolar lavage (BAL) fluid, and the wet lung weight at 7 days after intratracheal instillation of bleomycin. Histopathological studies revealed that treatment with Antileukinate markedly suppressed inflammatory cell infiltration and interstitial lung edema. The neutrophil counts in the BAL fluid were significantly decreased in the Antileukinate-treated group. The suppression of pulmonary edema was further confirmed by the reduction of wet lung weight and total protein concentration in the BAL fluid. These findings suggest that Antileukinate is able to inhibit acute lung injury by suppressing neutrophil mobilization induced by CXC-chemokines.
Chemokine receptor inhibitor, Antileukinate, suppressed ovalbumin-induced eosinophilic inflammation in the airway
Cytokine 2003 Jun 7;22(5):116-25.PMID:12842759DOI:10.1016/s1043-4666(03)00121-2.
Accumulating evidence suggests that eosinophils play an important role in the pathogenesis of allergic diseases. An eosinophil-active chemokine, eotaxin, and its receptor, C-C chemokine receptor 3, are particularly attractive as novel targets of immunological intervention for the disease. In this study, we examine the effects of a hexa-peptide (Ac-RRWWCR-NH(2)), Antileukinate, which we have previously defined as a potent inhibitor of CXC chemokine receptor 1 and 2, on eotaxin in vitro and in vivo. Antileukinate inhibited the binding of 125I-labeled human eotaxin to human eosinophils with an IC(50) of approximately 10 microM and eosinophil chemotaxis to human eotaxin was significantly inhibited by 10 microM of Antileukinate. We examined the effects of Antileukinate on eosinophil accumulation induced by intraperitoneal administration of murine eotaxin, and confirmed that Antileukinate is also active in the murine system. When Antileukinate was tested in ovalbumin-induced airway inflammation model in vivo, Antileukinate significantly inhibited eosinophil accumulation and allergen-induced increase in total protein in bronchoalveolar lavage fluids. Furthermore, Antileukinate suppressed fibrous thickening of submucosal tissue induced by chronic antigen challenge. These results suggest that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation, and that Antileukinate may be a promising tool to control allergic diseases.
Inhibition of GROalpha-induced human endothelial cell proliferation by the alpha-chemokine inhibitor Antileukinate
Cytokine 1999 Mar;11(3):231-8.PMID:10209071DOI:10.1006/cyto.1998.0418.
GROalpha, an autocrine mitogenic factor for melanoma cell lines, belongs to the superfamily of alpha-chemokines. Here, we report that GROalpha stimulates the growth of human umbilical vein endothelial cells (HUVEC) in vitro, with proliferation being significantly stimulated by 100 nM recombinant human (rh) GROalpha. Proliferation was significantly inhibited by 100 microg/ml anti- human GROalpha monoclonal antibody (mAb), while excess GROalpha restored the growth. The addition of rhIL-8, rhIP-10, anti-human IL-8 or anti-human ENA-78 mAbs did not alter HUVEC proliferation. [125I]IL-8 binding to HUVEC was saturable and inhibited by non-radioactively iodinated IL-8, but not non-iodinated IL-8. [125I]GROalpha binding was also inhibited by iodinated IL-8. Since these data suggested specific binding sites for alpha-chemokines on HUVEC, we tested the effect of Antileukinate, a potent alpha-chemokine receptor inhibitor, on [125I]GROalpha binding. Antileukinate inhibited GROalpha binding and suppressed HUVEC proliferation in a dose-dependent manner. Antileukinate was not cytotoxic, with no decrease in cell viability in the presence of 100 microM Antileukinate. These findings suggest that GROalpha is essential for HUVEC growth factor and that Antileukinate inhibits growth by preventing autocrine GROalpha receptor binding. This raises the interesting possibility of alpha-chemokine receptor inhibitors, such as Antileukinate, in the treatment of cancer where angiogenesis is an important factor for tumour growth.
Treatment with Antileukinate, a CXCR2 chemokine receptor antagonist, protects mice against acute pancreatitis and associated lung injury
Regul Pept 2007 Jan 10;138(1):40-8.PMID:17014919DOI:10.1016/j.regpep.2006.08.006.
Acute pancreatitis is a common, and as yet incurable, clinical condition, the incidence of which has been increasing over recent years. Chemokines are believed to play a key role in the pathogenesis of acute pancreatitis. We have earlier shown that treatment with a neutralizing antibody against CINC, a CXC chemokine, protects rats against acute pancreatitis-associated lung injury. The hexapeptide Antileukinate (Ac-RRWWCR-NH2) is a potent inhibitor of binding of CXC chemokines to the receptors (CXCR2). This study aims to evaluate the effect of treatment with Antileukinate on acute pancreatitis and the associated lung injury in mice. Acute pancreatitis was induced in adult male Swiss mice by hourly intra-peritoneal injections of caerulein (50 microg/kg/h) for 10 h. Antileukinate (52.63 mg/kg, s.c.) was administered to mice either 30 min before or 1 h after starting caerulein injections. Severity of acute pancreatitis was determined by measuring plasma amylase, pancreatic water content, pancreatic myeloperoxidase (MPO) activity, pancreatic macrophage inflammatory protein-2 (MIP-2) levels and histological examination of sections of pancreas. A rise in lung MPO activity and histological evidence of lung injury in lung sections was used as criteria for pancreatitis-associated lung injury. Treatment with Antileukinate protected mice against acute pancreatitis and associated lung injury, showing thereby that anti-chemokine therapy may be of value in this condition.
Synergistic protection against hyperoxia-induced lung injury by neutrophils blockade and EC-SOD overexpression
Respir Res 2012 Jul 20;13(1):58.PMID:22816678DOI:10.1186/1465-9921-13-58.
Background: Oxygen may damage the lung directly via generation of reactive oxygen species (ROS) or indirectly via the recruitment of inflammatory cells, especially neutrophils. Overexpression of extracellular superoxide dismutase (EC-SOD) has been shown to protect the lung against hyperoxia in the newborn mouse model. The CXC-chemokine receptor antagonist (Antileukinate) successfully inhibits neutrophil influx into the lung following a variety of pulmonary insults. In this study, we tested the hypothesis that the combined strategy of overexpression of EC-SOD and inhibiting neutrophil influx would reduce the inflammatory response and oxidative stress in the lung after acute hyperoxic exposure more efficiently than either single intervention. Methods: Neonate transgenic (Tg) (with an extra copy of hEC-SOD) and wild type (WT) were exposed to acute hyperoxia (95% FiO2 for 7 days) and compared to matched room air groups. Inflammatory markers (myeloperoxidase, albumin, number of inflammatory cells), oxidative markers (8-isoprostane, ratio of reduced/oxidized glutathione), and histopathology were examined in groups exposed to room air or hyperoxia. During the exposure, some mice received a daily intraperitoneal injection of Antileukinate. Results: Antileukinate-treated Tg mice had significantly decreased pulmonary inflammation and oxidative stress compared to Antileukinate-treated WT mice (p < 0.05) or Antileukinate-non-treated Tg mice (p < 0.05). Conclusion: Combined strategy of EC-SOD and neutrophil influx blockade may have a therapeutic benefit in protecting the lung against acute hyperoxic injury.