MK-571 sodium salt hydrate
(Synonyms: L-660711) 目录号 : GC14980
MK-571 钠盐水合物，作为白三烯 D4 作用的强效特异性拮抗剂，用于治疗哮喘。
Cas No.:115103-85-0
Sample solution is provided at 25 µL, 10mM.
MK-571 sodium salt hydrate, as a potent and specific antagonist of leukotriene D4 action, used for treatment of asthma[1].
In vitro test it shown that with 0.01-100 μM MK-571 reduced the export of 3H-S1P from erythrocytes in a concentration-dependent manner[2]. In vitro efficacy test it exhibited that 12.5-50 μM MK-571 in both aortic and brain derived ECs has more obvious supress-the efflux of agents rate than that of verapamil[3]. MK-571 has inhibition against LTC4 transport with IC50 of 1.0 μM[4].
In vivo, treatment with 8-32 mg/kg MK-571 intravenously in mice caused dose-dependent protection against acetic-acid-induced abdominal constriction with ED50 of 30 mg/kg[5]. In vivo, mice were instilled after endotoxin instillation at doses of 15, 35, or 50 mg/kg, MK-571 obviously inhibited the influx of inflammatory cells and reduced pro-inflammatory cytokines in BALF in a dose-dependent manner[6]. In addition, 10 ug/eye completely inhibited in vivo chemotactic responses to LTD4, and partially inhibited (54%) the responses to ovalbumin[7]. In vivo, pretreatment with 1 mg/kg MK-571 orally markedly inhibited the OA(ovalbumin)-induced EO (eosinophils) migration[8] . Treatment with 1 mg/kg/day MK-571 for at least 1 day after injury in a model of balloon catheter injury of rat carotid artery, MK-571 had effective inhibition of myointimal VSMC (vascular smooth muscle cell) proliferation, with a 58% reduction of 5-bromo-2'-deoxyuridine (BrdU) uptake in the neointima and 69% reduction of neointimal thickening[9].
References:
[1] Tocco DJ, et al. Interspecies differences in stereoselective protein binding and clearance of MK-571. Drug Metab Dispos. 1990 Jul-Aug;18(4):388-92.
[2] Christensen PM, et al. Apolipoprotein M mediates sphingosine-1-phosphate efflux from erythrocytes. Sci Rep. 2017 Nov 8;7(1):14983.
[3] Eilers M, et al. MRP (ABCC) transporters-mediated efflux of anti-HIV drugs, saquinavir and zidovudine, from human endothelial cells. Exp Biol Med (Maywood). 2008 Sep;233(9):1149-60.
[4] Schaub T, et al. ATP-dependent leukotriene export from mastocytoma cells. FEBS Lett. 1991 Feb 11;279(1):83-6.
[5] G?k S, et al. The antinociceptive effect of leukotriene D(4) receptor antagonist, MK-571, in mice: possible involvement of opioidergic mechanism. Eur J Pharmacol. 1999 Dec 15;386(2-3):195-200.
[6] Hao Q, et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles Decrease Lung Injury in Mice. J Immunol. 2019 Oct 1;203(7):1961-1972.
[7] Chan CC, et al. Eosinophil-eicosanoid interactions: inhibition of eosinophil chemotaxis in vivo by a LTD4-receptor antagonist. Eur J Pharmacol. 1990 Dec 4;191(3):273-80.
[8] Foster A, et al. Peptide leukotriene involvement in pulmonary eosinophil migration upon antigen challenge in the actively sensitized guinea pig. Int Arch Allergy Appl Immunol. 1991;96(3):279-84.
[9] Porreca E, et al. Cysteinyl leukotriene D4 induced vascular smooth muscle cell proliferation: a possible role in myointimal hyperplasia. Thromb Haemost. 1996 Jul;76(1):99-104.
| Cell experiment [1]: | |
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Cell lines |
MDCKII-MRP2 |
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Preparation Method |
Prior to the addition of calcein-AM, cells were pre-exposed to increasing concentrations of the MRP-inhibitors (20-100 µM), MK-571, montelukast, zafirlukast or probenecid, for 15 minutes. Cells were then incubated with calcein-AM (0.25µM) in the dark for 30 minutes at 37°C and 5% CO2. Cells were then washed 3 times in ice-cold PBS and calcein-retentions were determined by using an FLx 800 fluorimeter. |
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Reaction Conditions |
20-100 µM; 15 min |
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Applications |
In the MDCKII-MRP2 cells, pre-exposure to MK-571 showed a 3-fold increase in calcein retention, whereas montelukast coexposure showed almost a 5-fold increase. |
| Animal experiment [2]: | |
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Animal models |
Sprague-Dawley male rats |
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Preparation Method |
Sprague-Dawley male rats were divided into 3 study groups: a sham-operated group, a kidney I/R group, and a group treated with MK-571 before the kidney I/R injury: MK-571 (5 mg/kg) was administered intraperitoneally 15 minutes before ischemia and every 12 hours after reperfusion up to 24 hours. |
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Dosage form |
5 mg/kg; i.p. |
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Applications |
In MK-571-treated rats, Penh was muted during methacholine challenge test. Treatment with MK-571, a leukotriene D4 inhibitor, effectively attenuates airway hypersensitivity, pulmonary inflammatory response, and lung and kidney injury. |
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References: [1] Roy U, et al. Montelukast is a potent and durable inhibitor of multidrug resistance protein 2-mediated efflux of taxol and saquinavir. Biol Pharm Bull. 2009 Dec;32(12):2002-9. |
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| Cas No. | 115103-85-0 | SDF | |
| 别名 | L-660711 | ||
| 化学名 | 5-(3-(2-(7-Chloroquinolin-2-yl)ethenyl)phenyl)-8-dimethylcarbamyl-4,6-dithiaoctanoic acid sodium salt hydrate | ||
| Canonical SMILES | O=C([O-])CCSC(C1=CC=CC(/C=C/C2=NC3=CC(Cl)=CC=C3C=C2)=C1)SCCC(N(C)C)=O.[Na+] | ||
| 分子式 | C26H26ClN2NaO3S2·xH2O | 分子量 | 537.07 (anhydrous basis) |
| 溶解度 | ≥ 33 mg/mL in DMSO | 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 | 1.862 mL | 9.3098 mL | 18.6195 mL |
| 5 mM | 0.3724 mL | 1.862 mL | 3.7239 mL |
| 10 mM | 0.1862 mL | 0.931 mL | 1.862 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet