127373-66-4 Usage
Uses
Different sources of media describe the Uses of 127373-66-4 differently. You can refer to the following data:
1. Treatment of acute lung injury; acute respiratory distress syndrome (elastase inhibitor).
2. Sivelestat is an inhibitor of neutrophil elastase that prevents neutrophil extracellular trap formation and rescues mice from endotoxic shock. The inhibition of neutropil elastase by Sivelestat is a promising therapeutic strategy to inhibit glial scar and promote functional recovery by upregulating angiopoietin-1 after spinal cord injury.
General Description
A cell-permeable, potent, substrate-competitive, and highly specific inhibitor of neutrophil elastase (IC50 = 19-49 nM using rat, rabbit, hamster, human, and mouse leukocyte elastase). Displays about 100-fold greater selectivity over pancreatic elastase (IC50 = 5.6 μM) and is inactive against trypsin, thrombin, plasmin, kallikrein, chymotrypsin, and cathepsin G even at concentrations as high as 100 μM. Effectively suppresses human neutrophil elastase-induced lung hemorrhage and skin capillary permeability in vivo. Also reported to inhibit mast cell Stat6-protease.
Biological Activity
sivelestat (ono-5046) is a neutrophil elastase inhibitor.human neutrophil elastase is a protease that hydrolyzes most connective tissue components, and it has been reported to participate in the tissue injury of rheumatoid arthritis, emphysema, adult respiratory distress syndrome as well as septic shock.
Biochem/physiol Actions
Sivelestat is a competitive human neutrophil elastase (HNE) inhibitor (IC50 = 44 nM, Ki = 0.2 μM). It also inhibits leukocyte elastase obtained from rabbit, rat, hamster and mouse (IC50 = 19 to 49 nM). However, it does not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 μM. In in-vivo studies, it suppressed lung hemorrhage in hamster (ID50 = 82 μg/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil elastase.
in vitro
sivelestat was found to be able to competitively inhibit the human neutrophil elastase, and it could inhibit leukocyte elastase from rat, rabbit, mouse and hamster. whereas, sivelestat even at 100 microm could not inhibit thrombin, plasmin, trypsin, pancreas kallikrein, plasma kallikrein, chymotrypsin and cathepsin g [1].
in vivo
in animal study, 50 or 100 mg/kg sivelestat were immediately administered by i.p. injection after the surgical procedure to male sprague-dawley rats with bacterial infection caused by cecal ligation and puncture. results showed that in the untreated rats, the mean arterial pressure(map) and glomerular filtration rate(gfr) decreased, while serum blood urea nitrogen(bun) and neutrophil gelatinase-associated lipocalin(ngal) levels increased. sivelestat was found to promot the survival of the rats with sepsis, restored the impairment of map and gfr, and inhibited the increased bun and ngal levels. in addition, sivelestat could suppress the clp-induced macrophage infiltration in the rats [2].
IC 50
44 nm
references
[1] kawabata k,suzuki m,sugitani m,imaki k,toda m,miyamoto t. ono-5046, a novel inhibitor of human neutrophil elastase. biochem biophys res commun.1991 jun 14;177(2):814-20.[2] li g,jia j,ji k,gong x,wang r,zhang x,wang h,zang b. the neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats. int j mol med.2016 sep;38(3):767-75. [3] aikawa n,kawasaki y. clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of acute respiratory distress syndrome. ther clin risk manag.2014 aug 5;10:621-9.
Check Digit Verification of cas no
The CAS Registry Mumber 127373-66-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,7,3,7 and 3 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 127373-66:
(8*1)+(7*2)+(6*7)+(5*3)+(4*7)+(3*3)+(2*6)+(1*6)=134
134 % 10 = 4
So 127373-66-4 is a valid CAS Registry Number.
InChI:InChI=1/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)
127373-66-4Relevant articles and documents
TARGETED DELIVERY TO BETA CELLS
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Sheet 12/33, (2018/11/22)
The disclosure includes zinc prodrugs for targeted delivery of therapeutic, diagnostic or imaging agents to β-cells and methods of use therefor. The disclosure also includes targeted delivery of small molecules to β-cells that stabilize and activate CRISP
Efficient synthesis of sivelestat sodium hydrate
Bijukumar,Maloyesh,Sampat,Bhirud,Rajendra
, p. 1718 - 1724 (2008/09/20)
An efficient and scaleable synthesis of sivelestat sodium hydrate has been developed. Copyright Taylor & Francis Group, LLC.
Glycine derivative monosodium salt tetrahydrate
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, (2008/06/13)
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