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Purity: ≥98%
Sivelestat sodium, the sodium salt of Sivelestat (also known as ONO5046; LY544349; EI546), is a novel, potent and competitive inhibitor of human neutrophil elastase (HNE) with IC50 value of 44 nM and Ki of 200 nM; it also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse. ONO-5046 did not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 microM. In in vivo studies, ONO-5046 suppressed lung hemorrhage in hamster by intratracheal administration and increase of skin capillary permeability in guinea pig by intravenous administration. It is used in the treatment of acute respiratory failure. Preliminary studies show Sivelestat may also improve neuropathic pain.
| Targets |
Human neutrophil elastase(IC50 = 44 nM; Ki=200 nM)
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| ln Vitro |
Even at 100 μM, sivelestat (ONO-5046) does not inhibit chymotrypsin, cathepsin G, pancreatic kallikrein, thrombin, plasmin, plasma kallikrein, or plasma kallikrein[1]. The IC50 values of Sivelestat (ONO-5046) for human, rabbit, rat, hamster, and mouse neutrophil elastase are 44 nM, 36 nM, 19 nM, 37 nM, and 49 nM, respectively[1].
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| ln Vivo |
Human neutrophil elastase induces both the suppression of lung hemorrhage in hamsters (ID50 = 82 pg/kg) and the increase of skin capillary permeability in guinea pigs (ID50 = 9.6 mg/kg) when sedelestat (ONO-5046, 0.021-2.1 mg/kg, intratracheally) is administered intravenously[1]. In rats, sivelestat (10 mg/kg) infused via the tail vein reduces lung damage following hemorrhagic shock[2]. In the rat bladder, ivelestat (15, 60 mg/kg, ip) prevents ischemia-reperfusion injury[3].
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| Enzyme Assay |
ONO-5046, N-[2-[4-(2,2-Dimethylpropionyloxy)phenylsulfonylamino] aminoacetic acid, competitively inhibited human neutrophil elastase (IC50 = 0.044 microM, Ki = 0.2 microM). It also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse. However, ONO-5046 did not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 microM[1].
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| Animal Protocol |
Animal/Disease Models: Male Golden hamsters, weighing 90 to 110 g[1].
Doses: 0.021-2.1 mg/kg. Route of Administration: Intratracheally five min before HNE injection. Experimental Results: Dramatically and dosedependently suppressed the lung hemorrhage. Animal/Disease Models: Male SD (Sprague-Dawley) rats weighing 350-400 g[2]. Doses: 10 mg/kg. Route of Administration: Continuous infusion via the tail vein at 10 mg/kg/h for 60 min during the resuscitation phase. Experimental Results: Greatly suppressed lung injury, as revealed by the decreased histological damage. Dramatically ameliorated HSR-induced lung injury. Markedly diminished the levels of TNF-α and iNOS gene. Animal/Disease Models: Male Sprague Dawley rats, 8 weeks old and weighing 250-320 g[3]. Doses: 15 mg/kg or 60 mg/kg. Route of Administration: IP. Experimental Results: diminished the blood flow in the bladder during reperfusion phase compared to the IR group. |
| References |
[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.
[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. [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. [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 |
| Additional Infomation |
In the present study, we evaluated the effect of neutrophil elastase inhibitor, sivelestat sodium hydrate on ischemia-reperfusion injury in the rat bladder. Rat abdominal aorta was clamping with a small clip to induce ischemia-reperfusion injury in the bladder. Eight-week-old male Sprague Dawley rats were divided into four groups; sham-operated control rats, 30 min ischemia-60 min reperfusion (IR) rats, and IR rats treated with 15 or 60 mg/kg of sivelestat sodium hydrate. Sixty minutes prior to induction of ischemia, sivelestat sodium hydrate was administrated intraperitoneally. Real-time monitoring of blood flow and nitric oxide (NO) release were measured simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. The NO2-NO3 and malonaldehyde (MDA) concentrations were measured in the experimental urinary bladders. Clamping of the abdominal aorta, blood flow was rapidly decreased and NO release was gradually increased. After removing the clip, blood flow was rapidly increased and NO release was gradually returned to the basal level. These movements of blood flow and NO release were inhibited by treatment with sivelestat sodium hydrate in a dose-dependent manner. Both NO2-NO3 and MDA concentrations in the bladder were increased by induction of IR, and NO2-NO3 and MDA concentrations were decreased by treatment with high dose of sivelestat sodium hydrate significantly. Our data indicated that sivelestat sodium hydrate could inhibit increasing NO2-NO3 and MDA concentrations by IR, and it has potentiality protective effects on IR injury in the rat urinary bladder.[3]
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| Molecular Formula |
C₂₀H₂₁N₂NAO₇S
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|---|---|
| Molecular Weight |
456.44
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| Exact Mass |
456.09671
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| CAS # |
150374-95-1
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| Related CAS # |
Sivelestat;127373-66-4;Sivelestat sodium tetrahydrate;201677-61-4
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| PubChem CID |
23664980
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| Appearance |
Typically exists as white to off-white solids at room temperature
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| LogP |
2.46
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| tPSA |
150.08
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| SMILES |
[O-]C(CNC(C1=CC=CC=C1NS(C2=CC=C(OC(C(C)(C)C)=O)C=C2)(=O)=O)=O)=O.[Na+]
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| InChi Key |
ZAIFANJZUGNYCK-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C20H22N2O7S.Na/c1-20(2,3)19(26)29-13-8-10-14(11-9-13)30(27,28)22-16-7-5-4-6-15(16)18(25)21-12-17(23)24;/h4-11,22H,12H2,1-3H3,(H,21,25)(H,23,24);/q;+1/p-1
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| Chemical Name |
sodium;2-[[2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoyl]amino]acetate
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| Synonyms |
Sivelestat sodium, ONO5046-Na, Sodium sivelestat, EI546 sodium, LY544349 sodium; ONO5046, LY544349, EI546; ONO 5046; ONO5046; ONO-5046; LY544349; LY-544349; LY 544349; EI 546 sodium salt hydrate, Elaspol sodium salt hydrate, LY 544349 sodium salt hydrate, Trade name: Elaspol.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.48 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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