Sivelestat free acid | CAS#127373-66-4 | Human Neutrophil Elastase Inhibitor

MedKoo Cat#: 319921 | Name: Sivelestat free acid

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Sivelestat, also known as ONO 5046, is an inhibitor of human neutrophil elastase. It is used in the treatment of acute respiratory failure. Preliminary studies show Sivelestat may also improve neuropathic pain.

Chemical Structure

Sivelestat free acid

CAS#127373-66-4 (free acid)

Theoretical Analysis

MedKoo Cat#: 319921

Name: Sivelestat free acid

CAS#: 127373-66-4 (free acid)

Chemical Formula: C20H22N2O7S

Exact Mass: 434.1148

Molecular Weight: 434.46

Elemental Analysis: C, 55.29; H, 5.10; N, 6.45; O, 25.78; S, 7.38

Price and Availability

Size	Price	Availability
100mg	USD 250.00	2 weeks
250mg	USD 450.00	2 weeks
500mg	USD 750.00	2 weeks
1g	USD 1,250.00	2 weeks
2g	USD 2,050.00	2 weeks

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Related CAS #

127373-66-4 (free acid) 150374-95-1 (sodium) 201677-61-4 (sodium hydrate)

Synonym

ONO 5046; ONO5046; ONO-5046; LY544349; LY-544349; LY 544349; EI 546 sodium salt hydrate, Elaspol sodium salt hydrate, LY 544349 sodium salt hydrate, Sivelestat. Trade name: Elaspol.

IUPAC/Chemical Name

N-{2-[({4-[(2,2-Dimethylpropanoyl)oxy]phenyl}sulfonyl)amino]benzoyl}glycine

InChi Key

BTGNGJJLZOIYID-UHFFFAOYSA-N

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)

SMILES Code

O=C(O)CNC(C1=CC=CC=C1NS(=O)(C2=CC=C(OC(C(C)(C)C)=O)C=C2)=O)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in ethanol

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Sivelestat is a competitive inhibitor of human neutrophil elastase, with an IC50 of 44 nM and a Ki of 200 nM.

In vitro activity:

The combination of sivelestat and trastuzumab might be a novel therapeutic strategy for HER2-positive breast cancer. Sivelestat effectively suppressed the tumor progression mechanism initiated by neutrophil elastase (NE) through tumor growth factor-α (TGF-α) in breast cancer cells, while the impact of trastuzumab was hindered by TGF-α. However, the combination of trastuzumab and sivelestat resulted in more potent suppression of cell proliferation, overcoming the impairment by TGF-α on HER2 down-regulation. Reference: Anticancer Res. 2012 Jan;32(1):13-9. https://pubmed.ncbi.nlm.nih.gov/22213283/

In vivo activity:

Sivelestat attenuated AngII-induced abdominal aortic aneurysm through the inhibition of neutrophil elastase. In the 1-week study in male apolipoprotein E-deficient mice, AngII increased plasma and tissue elastase activity and aortic width, which were reduced by sivelestat. Sivelestat also decreased the incidence of abdominal aortic aneurysms and mitigated elastin fragmentation induced by AngII. Inflammatory cell accumulation and MMP-2/9 enhancement by AngII were reduced by sivelestat. Reference: Am J Hypertens. 2023 Nov 20:hpad107. https://pubmed.ncbi.nlm.nih.gov/37982444/

	Solvent	mg/mL	mM	comments
Solubility
	Ethanol	3.0	6.97

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 434.46 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium. Animals (Basel). 2020 May 16;10(5):863. doi: 10.3390/ani10050863. PMID: 32429399; PMCID: PMC7278485. 2. Nawa M, Osada S, Morimitsu K, Nonaka K, Futamura M, Kawaguchi Y, Yoshida K. Growth effect of neutrophil elastase on breast cancer: favorable action of sivelestat and application to anti-HER2 therapy. Anticancer Res. 2012 Jan;32(1):13-9. PMID: 22213283. 3. Hada Y, Uchida HA, Okamoto S, Otaka N, Katayama K, Subramanian V, Daugherty A, Wada J. Neutrophil Elastase Inhibition by Sivelestat (ONO-5046) Attenuates AngII-induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice. Am J Hypertens. 2023 Nov 20:hpad107. doi: 10.1093/ajh/hpad107. Epub ahead of print. PMID: 37982444. 4. Weng J, Liu D, Shi B, Chen M, Weng S, Guo R, Zhou X. Sivelestat sodium alleviated lipopolysaccharide-induced acute lung injury by improving endoplasmic reticulum stress. Gene. 2023 Oct 30;884:147702. doi: 10.1016/j.gene.2023.147702. Epub 2023 Aug 9. PMID: 37567453.

In vitro protocol:

In vivo protocol:

1. Hada Y, Uchida HA, Okamoto S, Otaka N, Katayama K, Subramanian V, Daugherty A, Wada J. Neutrophil Elastase Inhibition by Sivelestat (ONO-5046) Attenuates AngII-induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice. Am J Hypertens. 2023 Nov 20:hpad107. doi: 10.1093/ajh/hpad107. Epub ahead of print. PMID: 37982444. 2. Weng J, Liu D, Shi B, Chen M, Weng S, Guo R, Zhou X. Sivelestat sodium alleviated lipopolysaccharide-induced acute lung injury by improving endoplasmic reticulum stress. Gene. 2023 Oct 30;884:147702. doi: 10.1016/j.gene.2023.147702. Epub 2023 Aug 9. PMID: 37567453.

1: Xiao XG, Zu HG, Li QG, Huang P. Sivelestat sodium hydrate attenuates acute lung injury by decreasing systemic inflammation in a rat model of severe burns. Eur Rev Med Pharmacol Sci. 2016 Feb;20(3):528-36. PubMed PMID: 26914130. 2: Wang J, Dai XJ, Zhang YF, Zhong DF, Wu YL, Chen XY. [Simultaneous determination of sivelestat and its metabolite XW-IMP-A in human plasma using HPLC-MS/MS]. Yao Xue Xue Bao. 2015 Oct;50(10):1318-23. Chinese. PubMed PMID: 26837180. 3: Yamada K, Kobayashi H, Bo R, Takahashi T, Hasegawa Y, Nakamura M, Ishige N, Yamaguchi S. Elevation of pivaloylcarnitine by sivelestat sodium in two children. Mol Genet Metab. 2015 Nov;116(3):192-4. doi: 10.1016/j.ymgme.2015.09.009. Epub 2015 Sep 26. PubMed PMID: 26428892. 4: Miyoshi S, Ito R, Katayama H, Dote K, Aibiki M, Hamada H, Okura T, Higaki J. Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients. Drug Des Devel Ther. 2014 Sep 2;8:1211-9. doi: 10.2147/DDDT.S68030. eCollection 2014. PubMed PMID: 25214765; PubMed Central PMCID: PMC4159222. 5: 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. doi: 10.2147/TCRM.S65066. eCollection 2014. Review. PubMed PMID: 25120368; PubMed Central PMCID: PMC4130327. 6: Wang Y, Yang H, Hu Q, Hou Y, Luo H, Liu L. [Effects of sivelestat on acute lung injury in dogs with severe burn-blast combined injury]. Zhonghua Shao Shang Za Zhi. 2014 Apr;30(2):158-65. Chinese. PubMed PMID: 24989662. 7: Wang H, Wang S, Tang A, Gong H, Ma P, Chen L. Combined effects of sivelestat and resveratrol on severe acute pancreatitis-associated lung injury in rats. Exp Lung Res. 2014 Aug;40(6):288-97. doi: 10.3109/01902148.2014.908249. Epub 2014 May 2. PubMed PMID: 24785170. 8: Kohira S, Oka N, Inoue N, Itatani K, Kitamura T, Horai T, Oshima H, Tojo K, Yoshitake S, Miyaji K. Effect of additional preoperative administration of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass. Artif Organs. 2014 Dec;38(12):1018-23. doi: 10.1111/aor.12311. Epub 2014 Apr 21. PubMed PMID: 24750107. 9: Yuan Q, Jiang YW, Fang QH. Improving effect of Sivelestat on lipopolysaccharide-induced lung injury in rats. APMIS. 2014 Sep;122(9):810-7. doi: 10.1111/apm.12222. Epub 2014 Feb 1. PubMed PMID: 24484066. 10: Sakai S, Tajima H, Miyashita T, Nakanuma S, Makino I, Hayashi H, Nakagawara H, Kitagawa H, Fushida S, Fujimura T, Saito H, Munesue S, Yamamoto Y, Ohta T. Sivelestat sodium hydrate inhibits neutrophil migration to the vessel wall and suppresses hepatic ischemia-reperfusion injury. Dig Dis Sci. 2014 Apr;59(4):787-94. doi: 10.1007/s10620-013-2963-8. Epub 2013 Dec 8. PubMed PMID: 24318803. 11: Park JS, Park KH, Kim H, Choi SY. Effects of sivelestat treatment on acute lung injury in paraquat-intoxicated rats. Drug Chem Toxicol. 2014 Jan;37(1):114-20. doi: 10.3109/01480545.2013.834351. Epub 2013 Oct 11. PubMed PMID: 24111663. 12: Nomura N, Asano M, Saito T, Nakayama T, Mishima A. Sivelestat attenuates lung injury in surgery for congenital heart disease with pulmonary hypertension. Ann Thorac Surg. 2013 Dec;96(6):2184-91. doi: 10.1016/j.athoracsur.2013.07.017. Epub 2013 Sep 25. PubMed PMID: 24075485. 13: Kumagai K, Saikawa Y, Takeuchi H, Suda K, Fukuda K, Nakamura R, Takahashi T, Kawakubo H, Wada N, Miyasho T, Kitagawa Y. The neutrophil elastase inhibitor sivelestat suppresses accelerated gastrointestinal tumor growth via peritonitis after cecal ligation and puncture. Anticancer Res. 2013 Sep;33(9):3653-9. PubMed PMID: 24023292. 14: Matsuzaki K, Okumi M, Kishimoto N, Yazawa K, Miyagawa Y, Uchida K, Nonomura N. [A case of bladder cancer producing granulocyte colony-stimulating factor and interleukin-6 causing respiratory failure treated with neoadjuvant systemic chemotherapy along with sivelestat]. Hinyokika Kiyo. 2013 Jul;59(7):443-7. Japanese. PubMed PMID: 23945326. 15: Wang H, Tang AM, Liu D, Li G, Ye L, Li X, Li C, Chen L. Renoprotective activity of sivelestat in severe acute pancreatitis in rats. Exp Ther Med. 2013 Jul;6(1):29-32. Epub 2013 Apr 24. PubMed PMID: 23935713; PubMed Central PMCID: PMC3735895. 16: Eguchi T, Yoshida K, Kondo R, Hamanaka K, Shiina T, Komatsu Y, Yamamoto H, Kubo K, Hasegawa J, Koizumi T. Sivelestat prevents cytoskeletal rearrangements in neutrophils resulting from lung re-expansion following one-lung ventilation during thoracic surgery. Inflammation. 2013 Dec;36(6):1479-84. doi: 10.1007/s10753-013-9689-9. PubMed PMID: 23872720. 17: Kohira S, Oka N, Inoue N, Itatani K, Hanayama N, Kitamura T, Fujii M, Takeda A, Oshima H, Tojo K, Yoshitake S, Miyaji K. Effect of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass: a prospective randomized study. Artif Organs. 2013 Dec;37(12):1027-33. doi: 10.1111/aor.12103. Epub 2013 Jul 3. PubMed PMID: 23834653. 18: Cao J, Liu Q. Protective effects of sivelestat in a caerulein-induced rat acute pancreatitis model. Inflammation. 2013 Dec;36(6):1348-56. doi: 10.1007/s10753-013-9674-3. PubMed PMID: 23794035. 19: Inoue N, Oka N, Kitamura T, Shibata K, Itatani K, Tomoyasu T, Miyaji K. Neutrophil elastase inhibitor sivelestat attenuates perioperative inflammatory response in pediatric heart surgery with cardiopulmonary bypass. Int Heart J. 2013;54(3):149-53. PubMed PMID: 23774238. 20: Aune SE, Yeh ST, Kuppusamy P, Kuppusamy ML, Khan M, Angelos MG. Sivelestat attenuates myocardial reperfusion injury during brief low flow postischemic infusion. Oxid Med Cell Longev. 2013;2013:279847. doi: 10.1155/2013/279847. Epub 2013 May 22. PubMed PMID: 23766850; PubMed Central PMCID: PMC3674745.