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Reparixin L-lysine salt

现货
Catalog No.
A3753
CXCL8受体CXCR1/CXCR2活化的抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,800.00
现货
5mg
¥ 2,000.00
现货
10mg
¥ 3,280.00
现货
200mg
¥ 16,720.00
Ship with 10-15 days

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Background

Reparixin L-lysine salt is an inhibitor of interleukin 8 receptor alpha (CXCR1) and beta (CXCR2) with IC50 value of 5.6 nM and 80 nM respectively [1].

CXCR1 and 2 belong to class A of 7-transmembrane G protein coupled receptor, and they share 78% amino acid identity. They are specific receptors for interleukin-8 which is a chemokine. They are mainly expressed in the neutrophils, where they mediate neutrophil migration to the site of inflammation. In addition, they are also involved in tumor aggressive growth and metastasis of human malignant melanoma.

Structural and biochemical study identified that Reparixin L-lysine salt had non-competitive allosteric interaction with CXCR1 and 2, by which blocking CXCR1 and CXR2 in an inactive conformation, and thus suppressed receptor-induced intracellular signaling cascade and cellular response [2]. When CXCR1 were expressed in L1.2 cells, cell migration induced by 10 nM CXC8 was significantly inhibited by reparixin L-lysine salt [1].

In mouse model, treatment of reparixin L-lysine salt after introduction of injury significantly (15 mg/ kg/ day for 7 days) suppressed secondary degeneration by reducing CXC8-dependent oligodendrocyte apoptosis, migration to the injury site of neutrophils and ED-1-positive cells. Additionally, the level of macrophage-inflammatory protein-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1 beta was also reduced, and the proliferation of glial fibrillary acidic protein-positive cells was significantly reduced [2].

In mouse ischemia model, pre-treatment with reparixin reduced the motor deficits, myeloperoxidase activity and IL-1b level. Furthermore, ischemic injury was also attenuated [3].

References:
[1] Moriconi A et al. , Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007, 50(17): 3984-4002.
[2] Gorio A, Madaschi L, Zadra G, Reparixin, an inhibitor of CXCR2 function, attenuates inflammatory responses and promotes recovery of functionafter traumatic lesion to the spinal cord.  J Pharmacol Exp Ther. 2007, 322(3): 973-981.
[3] Sousa L F, Coelho F M, Rodrigues D H, Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice.  Clinics (Sao Paulo). 2013, 68(3): 391-394.

文献引用

1. Sharma I, Singh A, et al. "IL-8/CXCR1/2 signalling promotes tumor cell proliferation, invasion and vascular mimicry in glioblastoma." J Biomed Sci. 2018 Aug 8;25(1):62. PMID:30086759

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt429.57
Cas No.266359-93-7
FormulaC20H35N3O5S
SynonymsRepertaxin L-lysine salt
Solubility≥21.5 mg/mL in DMSO, ≥66.67 mg/mL in EtOH, ≥16.67 mg/mL in H2O with gentle warming
Chemical Name(2S)-2,6-diaminohexanoic acid;(2R)-2-[4-(2-methylpropyl)phenyl]-N-methylsulfonylpropanamide
SDFDownload SDF
Canonical SMILESCC(C)CC1=CC=C(C=C1)C(C)C(=O)NS(=O)(=O)C.C(CCN)CC(C(=O)O)N
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验[1]:

结合实验

将分离的PMN(107×mL)重悬于RPMI 1640中,并在存在repertaxin(1 mM)或载体的情况下于37℃下孵育15分钟。孵育后,在repertaxin或载体存在下,将细胞(2×107/ml)重悬于结合培养基(10 mg/ml BSA、20 mM HEPES和0.02% NaN3的RPMI 1640)。将等分试样的0.2 nM [125I]CXCL8和未标记的CXCL8的系列稀释液加入到100 μL结合培养基中的106个细胞中,温和搅拌下室温温育1小时。通过在微量离心机上通过油层梯度(80%硅和20%石蜡)离心,将未结合的放射性与细胞结合的放射性分离。通过200倍摩尔过量的未标记的CXCL8测定非特异性结合。使用LIGAND程序进行Scatchard分析。

细胞实验[1]:

细胞系

人多形核细胞(PMN)和单核细胞,啮齿动物腹膜PMN

溶解方法

溶于DMSO。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

45 min (人PMN),1 h (啮齿动物PMN),2 h (单核细胞)

实验结果

Repertaxin抑制CXCL8和CXCL1诱导的人类PMN迁移,IC50分别为1 nM和400 nM,这分别由CXCR1和CXCR2介导。Repertaxin还抑制由CXCL1和CXCL2诱导的啮齿动物PMN的趋化性。

动物实验[2]:

动物模型

肝脏后缺血RI大鼠模型

剂量

3、15或30 mg/kg;再灌注前15分钟(i.v.),再灌注后2小时(s.c.)。

实验结果

Repertaxin(15 mg/kg)抑制90%的PMN募集到再灌注肝脏,显著减少肝损伤。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Bertini R, Allegretti M, Bizzarri C, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl AcadSci U S A, 2004, 101(32): 11791-11796.

质量控制

化学结构

Reparixin L-lysine salt

相关生物数据

Reparixin L-lysine salt