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Sivelestat sodium salt

白细胞弹性蛋白酶抑制剂，Sivelestat(ONO5046; LY544349; EI546)钠盐是人中性白细胞弹性蛋白酶（NE neutrophil elastase）竞争性抑制剂，IC50和Ki分别为44 nM和为200 nM，还能抑制来自于兔、鼠、仓鼠的白细胞弹性蛋白酶。

目录号: PC15694 纯度: ≥98%

CAS No. :150374-95-1

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中文名称	Sivelestat sodium salt
中文别名	西维来司钠;N-[2-[[[4-(2,2-二甲基-1-氧代丙氧基)苯基]磺酰]氨基]苯甲酰]-(S)-甘氨酸单钠盐;西维来司他钠
英文名称	Sivelestat sodium salt
英文别名	Sivelestat sodium;N-[2-[[[4-(2,2-Dimethyl-1-oxopropoxy)phenyl]sulfonyl]amino]benzoyl]-(S)-glycine monosodium salt;Sivelestat sodium salt;sodium,2-[[2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoyl]amino]acetate;EI546 sodium;HMS3262D11;LY544349 sodium;ONO-5046.Na;ONO5046-Na;Sivelestat sodium salt hydrate;Sodium sivelestat;Sivelestat SodiuM anhydrous;N-{2-[({4-[(2,2-Dimethylpropanoyl)oxy]phenyl}sulfonyl)amino]benzoyl}glycinesodiumsalt;Glycine, N-[2-[[[4-(2,2-diMethyl-1-oxopropoxy)phenyl]sulfonyl]aMino]benzoyl]-, MonosodiuM salt
Cas No.	150374-95-1
分子式	C₂₀H₂₁N₂O₇S-^.Na+
分子量	456.44
包装储存	4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

生物活性

Sivelestat (EI546) sodium is a competitive inhibitor of human neutrophil elastase, with an IC₅₀ of 44 nM and a K_i of 200 nM. Sivelestat (EI546) sodium has the potential for the study of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19.

性状

Solid

体外研究(In Vitro)

Sivelestat (ONO-5046) does not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 μM.
Sivelestat (ONO-5046) exhibits IC₅₀ values of 44 nM, 36 nM, 19 nM, 37 nM and 49 nM for human, rabbit, rat, hamster and mouse neutrophil elastase, respectively.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究(In Vivo)

Sivelestat (ONO-5046, 0.021-2.1 mg/kg, intratracheally) suppresses lung hemorrhage in hamster (ID₅₀ = 82 pg/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID₅₀ = 9.6 mg/kg) by intravenous administration, both of which are induced by human neutrophil elastase.
Sivelestat (10 mg/kg, infusion via the tail vein) ameliorates lung injury after hemorrhagic shock in rats.
Sivelestat (15, 60 mg/kg, ip) prevents ischemia–reperfusion injury in the rat bladder.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Male Golden hamsters, weighing 90 to 110 g.
Dosage:	0.021-2.1 mg/kg.
Administration:	Intratracheally five min before HNE injection.
Result:	Significantly and dosedependently suppressed the lung hemorrhage.

Animal Model:	Male Sprague-Dawley rats weighing 350-400 g.
Dosage:	10 mg/kg.
Administration:	Continuous infusion via the tail vein at 10 mg/kg/h for 60 min during the resuscitation phase.
Result:	Greatly suppressed lung injury, as revealed by the reduced histological damage. Significantly ameliorated HSR-induced lung injury. Markedly decreased the levels of TNF-α and iNOS gene.

Animal Model:	Male Sprague Dawley rats, 8 weeks old and weighing 250-320 g.
Dosage:	15 mg/kg or 60 mg/kg.
Administration:	IP.
Result:	Decreased the blood flow in the bladder during reperfusion phase compared to the IR group.

运输条件

Room temperature or refrigerated transportation.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

ClinicalTrial

参考文献

[1]. Kawabata K, et al. ONO-5046, a novel inhibitor of human neutrophil elastase. Biochem Biophys Res Commun. 1991 Jun 14;177(2):814-20. [Information]

[2]. Yuichiro Toda, et al. A neutrophil elastase inhibitor, sivelestat, ameliorates lung injury after hemorrhagic shock in rats. Int J Mol Med. 2007 Feb;19(2):237-43. [Information]

[3]. Tomoharu Kono, et al. Neutrophil elastase inhibitor, sivelestat sodium hydrate prevents ischemia-reperfusion injury in the rat bladder. Mol Cell Biochem. 2008 Apr;311(1-2):87-92. [Information]

[4]. Adeleh Sahebnasagh, et al. Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19. J Clin Pharm Ther. 2 [Information]

溶解度数据

体外研究:

DMSO : 100 mg/mL (219.09 mM; Need ultrasonic)

H₂O : 1 mg/mL (2.19 mM; ultrasonic and warming and heat to 80°C)

配制储备溶液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.1909 mL	10.9543 mL	21.9087 mL
5 mM	0.4382 mL	2.1909 mL	4.3817 mL
10 mM	0.2191 mL	1.0954 mL	2.1909 mL

产品不同，其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液；配成溶液后，建议分装保存，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, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，建议在 6 个月内使用，-20°C 储存时，建议在 1 个月内使用。

体内研究:

建议根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都建议先按照 体外研究 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

建议依照次序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (5.48 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.48 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH?O 中，得到澄清透明的生理盐水溶液
2.

建议依照次序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (5.48 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.48 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

建议依照次序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (5.48 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.48 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

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Data Sheet

1：一般建议：溶解度为Medlife测试数据，可能与文献描述存在差异。这是由于生产工艺和批次不同产生的正常现象。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。不同批次产品溶解度各有差异，仅做参考，具体以实验方案为准。

2：储存条件：粉末-20°C一般情况可以保存3年，溶于溶剂-80°C一般情况可以保存1年。不同产品及不同批次产品可能存在差异，请细致阅读产品信息，并辅助参考相关文献描述。

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