Reparixin L-lysine salt
(Synonyms: REPERTAXINL-赖氨酸盐,Repertaxin L-lysine salt) 目录号 : GC13813
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Reparixin L-lysine salt是一种参与炎症反应的CXCR1和CXCR2趋化因子受体的小分子变构非竞争性抑制剂。
Cas No.:266359-93-7
Sample solution is provided at 25 µL, 10mM.
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Reparixin L-lysine salt is a small molecule, allosteric noncompetitive inhibitor of CXCR1 and CXCR2 chemokine receptors involved in inflammation[1]. Reparixin is 400 folds more effective than CXCR2 in inhibiting CXCR1 activity[2]. Reparixin efficiently inhibits the biological events triggered by CXCL8 by binding to the transmembrane (TM) region of CXCR1 in an allosteric cavity within the helixes TM1, 2, 3, 6 and 7[2].
In vitro, the sensitivity to Reparixin-mediated inhibition of CXCL8-induced chemotaxis was reduced in L1.2 cells transfected with the mutant CXCR1 (Ile43Val) (IC50 values of 5.6×10-9M and 8.0×10-8M for CXCR1 WT and CXCR1 Ile43Val, respectively)[3]. The IC50 values of Reparixin for inhibiting CINC-1 and CXCL8-induced rat neutrophil migration were 6 and 30nM, respectively[4].
In vivo, Reparixin (3-30mg/kg; i.v.) inhibited, in a dose-dependent manner, the increase in vascular permeability in the intestine and lungs and the recruitment of neutrophils after ischemic SMA reperfusion in mice[4]. Reparixin treatment at 30mg/kg subcutaneously alleviated PM and bleomycin-induced pulmonary fibrosis phenotypes in mice[5].
References:
[1] Marsh DR, Flemming JM. Inhibition of CXCR1 and CXCR2 chemokine receptors attenuates acute inflammation, preserves gray matter and diminishes autonomic dysreflexia after spinal cord injury. Spinal Cord. 2011;49(3):337-344.
[2] Bertini R, Barcelos LS, Beccari AR, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2 non-competitive allosteric inhibitor. Br J Pharmacol. 2012;165(2):436-454.
[3] Moriconi A, Cesta MC, Cervellera MN, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007;50(17):3984-4002.
[4] Souza DG, Bertini R, Vieira AT, et al. Repertaxin, a novel inhibitor of rat CXCR2 function, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury. Br J Pharmacol. 2004;143(1):132-142.
[5] Cheng IY, Liu CC, Lin JH, et al. Particulate Matter Increases the Severity of Bleomycin-Induced Pulmonary Fibrosis through KC-Mediated Neutrophil Chemotaxis. Int J Mol Sci. 2019;21(1):227.
Reparixin L-lysine salt是一种参与炎症反应的CXCR1和CXCR2趋化因子受体的小分子变构非竞争性抑制剂[1]。Reparixin抑制CXCR1活性的效率是CXCR2的400倍[2]。Reparixin能够通过与CXCR1蛋白的跨膜区域（位于TM1、2、3、6和7螺旋结构内的别构腔）结合的方式，有效地抑制由CXCL8引发的生物过程[2]。
体外实验中，在转染了突变型 CXCR1（Ile43Val）的L1.2细胞中，Reparixin对CXCL8诱导的细胞趋化作用的抑制敏感性降低（CXCR1 WT和CXCR1 Ile43Val的IC50值分别为5.6×10-9M和8.0×10-8M）[3]。Reparixin抑制CINC-1和CXCL8诱导的大鼠嗜中性粒细胞迁移的IC50值分别为6和30nM[4]。
体内实验中，Reparixin（3-30mg/kg；静脉注射）以剂量依赖的方式抑制小鼠SMA缺血再灌注后肠和肺血管通透性的增加和中性粒细胞的募集[4]。Reparixin以30mg/kg皮下注射给药，可减轻小鼠中由颗粒物（PM）和博来霉素（bleomycin） 诱导的肺纤维化表型。
| Cell experiment [1]: | |
Cell lines | L1.2 cells |
Preparation Method | Wild-type CXCR1 and mutant CXCR1 I43V were transiently transfected via electroporation in L1.2 cells. Cells were preincubated overnight in growth medium containing 5mM sodium butyrate to maximize receptor expression, then pretreated for 30min at 37°C with 1-1000nM concentrations of Reparixin. After treatment, cell suspension were placed onto each Transwell filter containing 10nM CXCL8. After 4h of incubation at 37°C, the upper chamber was removed and the number of migrated cells was evaluated in a Bu¨rker chamber. |
Reaction Conditions | 1-1000nM; 4.5h |
Applications | Wild-type CXCR1/L1.2 transfectants migration induced by CXCL8 (10nM) was significantly inhibited by Reparixin, the inhibition being concentration-dependent and reaching the maximum (80%) at 0.1µM of Reparixin. The efficacy of reparixin was significantly lower in cells expressing Ile43Val CXCR1 mutant. |
| Animal experiment [2]: | |
Animal models | Male Wistar rats model of mild intestinal reperfusion injury |
Preparation Method | Reparixin was administered i.v. just prior to the reperfusion of the superior mesenteric artery (SMA). Investigated the dose-dependent effects of Reparixin treatment on increased intestinal and pulmonary vascular permeability and neutrophil recruitment. |
Dosage form | 3-30mg/kg; i.v. |
Applications | Postischaemic treatment of animals with Reparixin inhibited in a dose-dependent manner both the increase in vascular permeability and the recruitment of neutrophils in the intestine and lungs following reperfusion of the ischaemic SMA. Moreover, 50% inhibition only occurred when doses greater than 10mg/kg were used and the drug was equieffective and markedly prevented tissue injury when used at 30mg/kg. |
References: | |
| Cas No. | 266359-93-7 | SDF | |
| 别名 | REPERTAXINL-赖氨酸盐,Repertaxin L-lysine salt | ||
| 化学名 | (2S)-2,6-diaminohexanoic acid;(2R)-2-[4-(2-methylpropyl)phenyl]-N-methylsulfonylpropanamide | ||
| Canonical SMILES | CC(C)CC1=CC=C(C=C1)C(C)C(=O)NS(=O)(=O)C.C(CCN)CC(C(=O)O)N | ||
| 分子式 | C20H35N3O5S | 分子量 | 429.57 |
| 溶解度 | ≥ 21.5 mg/mL in DMSO, ≥ 66.67 mg/mL in EtOH, ≥ 16.67 mg/mL in Water with gentle warming | 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 | 2.3279 mL | 11.6395 mL | 23.2791 mL |
| 5 mM | 465.6 μL | 2.3279 mL | 4.6558 mL |
| 10 mM | 232.8 μL | 1.164 mL | 2.3279 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。
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet