| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
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
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| ln Vitro |
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| ln Vivo |
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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[3].
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| Cell Assay |
Background: Sivelestat sodium hydrate (sivelestat) is a specific neutrophil elastase inhibitor that is effective in treating acute lung injury associated with systemic inflammatory response syndrome. As such, it may be useful in treating hepatic ischemia-reperfusion injury (IRI), a condition in which neutrophils transmigrate into the interstitium, leading to release of neutrophil elastase from neutrophils and consequent damage to the affected tissue, particularly in cases of hepatic failure after liver transplantation or massive liver resection.[2]
Aims: The purpose of this study was to examine whether treatment with sivelestat inhibits neutrophil adhesion and migration to the vessel wall and suppresses hepatic IRI.[2] Methods: Whether and, if so, the extent to which sivelestat suppresses the adhesion and migration of neutrophils and reduces liver damage in hepatic IRI was examined in a human umbilical vein endothelial cell (HUVEC) model and a rat hepatic IRI model.[2] Results: In the HUVEC model, the extent of the adhesion and migration of neutrophils stimulated by platelet-activating factor were found to be dose-dependently inhibited by sivelestat treatment (p < 0.05). In the rat model, serum liver enzyme levels were significantly lower at 12 h after reperfusion, and the number of neutrophils that had migrated to extravascular sites was significantly less in the treatment group compared to the control group (p < 0.05).[2] Conclusion: Sivelestat inhibits the adhesion and migration of neutrophils to vascular endothelium in hepatic IRI, thereby suppressing liver injury.[2] |
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| Animal Protocol |
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| References |
[1]. Interact Cardiovasc Thorac Surg.2008 Oct;7(5):785-.
[2]. Dig Dis Sci.2014 Apr;59(4):787-94. [3]. Biochem Biophys Res Commun. 1991 Jun 14;177(2):814-20. |
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| Additional Infomation |
Sivelestat is a N-acylglycine and a pivalate ester. It is functionally related to a N-benzoylglycine.
Sivelestat has been used in trials studying the treatment of Acute Lung Injury and Respiratory Distress Syndrome, Adult. |
| Molecular Formula |
C20H22N2O7S
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|---|---|
| Molecular Weight |
434.46
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| Exact Mass |
434.11
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| Elemental Analysis |
C, 55.29; H, 5.10; N, 6.45; O, 25.78; S, 7.38
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| CAS # |
127373-66-4
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| Related CAS # |
Sivelestat sodium;150374-95-1;Sivelestat sodium tetrahydrate;201677-61-4
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| PubChem CID |
107706
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.598
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| LogP |
2.96
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| tPSA |
147.25
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| SMILES |
CC(C)(C)C(OC1=CC=C(S(=O)(NC2=CC=CC=C2C(NCC(O)=O)=O)=O)C=C1)=O
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| InChi Key |
BTGNGJJLZOIYID-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N2O7S/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)
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| Chemical Name |
N-{2-[({4-[(2,2-Dimethylpropanoyl)oxy]phenyl}sulfonyl)amino]benzoyl}glycine
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| Synonyms |
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.Ono-5046; 331731-18-1; 2-[[2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoyl]amino]acetic acid; ONO5046; LY544349; ABT-D2E7;
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : 87~100 mg/mL ( 200.24~230.17 mM )
Ethanol : 3.03 ~8 mg/mL(~6.97 mM ) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.75 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 (5.75 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 (5.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5% DMSO+ 40% PEG300+ 5% Tween 80+ 50% ddH2O: 3.25mg/ml (7.48mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3017 mL | 11.5085 mL | 23.0171 mL | |
| 5 mM | 0.4603 mL | 2.3017 mL | 4.6034 mL | |
| 10 mM | 0.2302 mL | 1.1509 mL | 2.3017 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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