Sivelestat (EI546) sodium 是竞争性的人类中性粒细胞弹性蛋白酶的抑制剂，其IC50值为 44 nM，Ki值为 200 nM。Sivelestat (EI546) sodium 有潜力用于COVID-19 的急性肺损伤/急性呼吸窘迫综合征或弥散性血管内凝血的研究。
| 生物活性 | Sivelestat (EI546) sodium is a competitive inhibitor ofhuman neutrophilelastase, with anIC50of 44 nM and aKiof 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[1][2][3][4]. |
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[1].
Sivelestat (ONO-5046) exhibits IC50values of 44 nM, 36 nM, 19 nM, 37 nM and 49 nM for human, rabbit, rat, hamster and mouse neutrophil elastase, respectively[1].
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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[1].
Sivelestat (10 mg/kg, infusion via the tail vein) ameliorates lung injury after hemorrhagic shock in rats[2].
Sivelestat (15, 60 mg/kg, ip) prevents ischemia–reperfusion injury in the rat bladder[3].
| Animal Model: | Male Golden hamsters, weighing 90 to 110 g[1]. | | 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[2]. | | 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.
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| Animal Model: | Male Sprague Dawley rats, 8 weeks old and weighing 250-320 g[3]. | | 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. |
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| Clinical Trial | |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 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) |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(219.09 mM;Need ultrasonic) H2O : 1 mg/mL(2.19 mM;ultrasonic and warming and heat to 80℃) 配制储备液 | 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 |
*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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro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. 请依序添加每种溶剂： 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 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。 *以上所有助溶剂都可在本网站选购。
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