SIVELESTAT

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H22N2O7S
Molecular Weight	434.463
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)C(=O)OC1=CC=C(C=C1)S(=O)(=O)NC2=CC=CC=C2C(=O)NCC(O)=O

InChI

InChIKey=BTGNGJJLZOIYID-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C20H22N2O7S
Molecular Weight	434.463
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25120368 | https://www.ncbi.nlm.nih.gov/pubmed/21088343 | http://adisinsight.springer.com/drugs/800003033 | https://www.ncbi.nlm.nih.gov/pubmed/2049103

Sivelestat is a neutrophil elastase inhibitor approved in Japan and the Republic of Korea for acute lung injury, including acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. Sivelestat is marketed as Elaspol in Japan. Sivelestat competitively inhibited human neutrophil elastase (IC50 = 0.044 uM, Ki = 0.2 uM). It also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Leukocyte elastase 19 Target ID: CHEMBL248 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2049103 \| https://www.ncbi.nlm.nih.gov/pubmed/21741848	Inhibitor 8504		0.044 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute lung injury 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25120368 https://www.ncbi.nlm.nih.gov/pubmed/15286546	Primary		Approved 8583	Elaspol Approved Use Acute lung injury associated with septicaemia Launch Date 2001

C_max

Value	Dose	Analyte	Population
11.678 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/730119_3999422D1020_2_001_1F.pdf#page=41 \| https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=27	0.5 mg/kg/h single, intravenous dose: 0.5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.883 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/730119_3999422D1020_2_001_1F.pdf#page=41 \| https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=27	1 mg/kg/h single, intravenous dose: 1 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.365 μg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=31	0.5 mg/kg/h 2 times / day multiple, intravenous dose: 0.5 mg/kg/h route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.08 μg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=31	0.5 mg/kg/h 2 times / day multiple, intravenous dose: 0.5 mg/kg/h route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.588 μg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=45	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.308 μg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=45	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
17.575 μg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=49	1 mg/kg 2 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
19.68 μg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=49	1 mg/kg 2 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
61.113 μg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/730119_3999422D1020_2_001_1F.pdf#page=41 \| https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=27	0.5 mg/kg/h single, intravenous dose: 0.5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
136.864 μg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/730119_3999422D1020_2_001_1F.pdf#page=41 \| https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=27	1 mg/kg/h single, intravenous dose: 1 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
59.06 μg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=31	0.5 mg/kg/h 2 times / day multiple, intravenous dose: 0.5 mg/kg/h route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
31.0376 μg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=45	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
59.5 μg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=45	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
55.364 μg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=49	1 mg/kg 2 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
390.9 min OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/730119_3999422D1020_2_001_1F.pdf#page=41 \| https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=27	0.5 mg/kg/h single, intravenous dose: 0.5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
350.7 min OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/730119_3999422D1020_2_001_1F.pdf#page=41 \| https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=27	1 mg/kg/h single, intravenous dose: 1 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
374.3 min OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=31	0.5 mg/kg/h 2 times / day multiple, intravenous dose: 0.5 mg/kg/h route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
220.9 min OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=45	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
238.9 min OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=45	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
265.9 min OTHER GOV'T https://www.pmda.go.jp/drugs/2002/P200200016/18018800_21400AMZ00459_X100_1.pdf#page=49	1 mg/kg 2 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIVELESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.4% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/730119_3999422D1020_2_001_1F.pdf#page=42			SIVELESTAT serum	Homo sapiens

Doses

Dose	Population	Adverse events
4.8 mg/kg/day 1 times / day multiple, intravenous Highest studied dose Dose: 4.8 mg/kg/day, 1 times / day Route: intravenous Route: multiple Dose: 4.8 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16688053/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16688053/	Sources: https://pubmed.ncbi.nlm.nih.gov/16688053/

PubMed

Title	Date	PubMed
Design, synthesis and evaluation of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase.	2011-08-01	21741848
Suppressive effects of sivelestat on interleukin 8 and TNF-α production from LPS-stimulated granulocytes in whole blood culture.	2010-12	20976506
Neutrophil elastase inhibitor restores gut ischemia reperfusion-induced impairment of gut immunity with reduced plasma interleukin-6 concentrations in mice.	2010-12	20969469
Prognostic impact of clinical course-specific mRNA expression profiles in the serum of perioperative patients with esophageal cancer in the ICU: a case control study.	2010-10-22	20969744
In vivo efficacy of sivelestat in combination with pazufloxacin against Legionella pneumonia.	2010-10	20939755
Effect of a selective neutrophil elastase inhibitor on early recovery from body water imbalance after transthoracic esophagectomy.	2010-09	20353442
Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine.	2010-08	20464430
Neutrophil elastase inhibitor prevents ischemic brain damage via reduction of vasogenic edema.	2010-07	20485441
Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats.	2010-06	20478544
Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass.	2010-06	20354035
The protective function of neutrophil elastase inhibitor in liver ischemia/reperfusion injury.	2010-05-15	20160675
Neutrophil elastase inhibitor improves survival of rats with clinically relevant sepsis.	2010-05	19953005
Extracorporeal immune therapy with immobilized agonistic anti-Fas antibodies leads to transient reduction of circulating neutrophil numbers and limits tissue damage after hemorrhagic shock/resuscitation in a porcine model.	2010-04-20	20406470
Efficacy of neutrophil elastase inhibitor on type A acute aortic dissection.	2010-04	20376727
The impact of oxidative stress levels on the clinical effectiveness of sivelestat in treating acute lung injury: an electron spin resonance study.	2010-04	20065874
Sivelestat (selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagulation patients.	2010-01	19487982
Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis.	2010	21088343
Mechanical strength and viscoelastic response of the periodontal ligament in relation to structure.	2010	20948569
DAMPening inflammation by modulating TLR signalling.	2010	20706656
Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion.	2010	20218909
Effects of elastase inhibitor on the epithelial cell apoptosis in bleomycin-induced pulmonary fibrosis.	2009-12	19995276
Prevention of leukocyte activation by the neutrophil elastase inhibitor, sivelestat, in the hepatic microcirculation after ischemia-reperfusion.	2009-08	19482311
A pilot randomized study of the neutrophil elastase inhibitor, Sivelestat, in patients undergoing cardiac surgery.	2009-08	19447800
Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia.	2009-06	19279053
Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB.	2009-04	19169649
Neutrophil elastase activity compensates for a genetic lack of matrix metalloproteinase-9 (MMP-9) in leukocyte infiltration in a model of experimental peritonitis.	2009-03	19088179
Sivelestat treatment for acute respiratory distress syndrome in an infant.	2009	19444574
Resuscitation of haemorrhagic shock with normal saline vs. lactated Ringer's: effects on oxygenation, extravascular lung water and haemodynamics.	2009	19257901
Plasma neutrophil elastase and elafin imbalance is associated with acute respiratory distress syndrome (ARDS) development.	2009	19197381
Inhibition of neutrophil elastase reduces lung injury and bacterial count in hamsters.	2008-12	18992355
[Efficacy of sivelestat for acute lung injury due to severe bacterial pneumonia with systemic inflammatory response syndrome].	2008-10	19044028
[Case of transfusion-related acute lung injury associated with severe intraoperative hypoxemia].	2008-10	18975546
Sivelestat attenuates postoperative pulmonary dysfunction after total arch replacement under deep hypothermia.	2008-10	18722781
Protective effect of sivelestat sodium (Eraspol) on postoperative lung dysfunction in patients with type A acute aortic dissection: a pilot study.	2008-10	18670380
The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model.	2008-10	18596053
Role of neutrophil elastase in development of pulmonary vascular injury and septic shock in rats.	2008-10	18323746
Usefulness of a selective neutrophil elastase inhibitor (sivelestat) in septic ARDS patients after gastrointestinal surgery.	2008-08-19	18705309
A neutrophil elastase inhibitor, sivelestat, reduces lung injury following endotoxin-induced shock in rats by inhibiting HMGB1.	2008-08	18536984
Continuous infusion of sivelestat sodium hydrate prevents lipopolysaccharide-induced intestinal paralysis and hypotension in conscious guinea-pigs.	2008-07	18346172
Protective effect of Sivelestat in a porcine hepatectomy model prepared using an intermittent Pringle method.	2008-06-10	18374331
[Effect of sivelestat sodium on acute lung injury after acute aortic dissection].	2008-06	18536289
Sivelestat and its role in tissue reperfusion injury.	2008-06	18450465
Neutrophil elastase activity in acute lung injury and respiratory distress syndrome.	2008-06	18410258
Sivelestat relaxes porcine coronary artery via inhibition of Ca2+ sensitization induced by a receptor agonist.	2008-05	18437095
[A case of lung adenocarcinoma effectively treated with sivelestat and corcicosteroid for drug-induced lung disease due to gefitinib].	2008-03	18409572
Beneficial effect of neutrophil elastase inhibitor on anti-Thy1.1 nephritis in rats.	2008-02	18199098
A neutrophil elastase inhibitor, sivelestat, improved respiratory and cardiac function in pediatric cardiovascular surgery with cardiopulmonary bypass.	2008	19011770
Neutrophil Proteases Activate Eosinophil Function in vitro.	2008	18504401
Severe Legionnaires' disease successfully treated using a combination of fluoroquinolone, erythromycin, corticosteroid, and sivelestat.	2008	18421197
Effects of sivelestat sodium hydrate on the reduction of radiation pneumonitis.	2007-12	17982688

Patents

Sample Use Guides

In Vivo Use Guide

0.2 mg/kg/hr continuous i.v. infusion - up to 14 days

Route of Administration: Intravenous

In Vitro Use Guide

Addition of 10 or 100 ug/ml sivelestat significantly (P < 0.05) inhibited the production of TNF-α from granulocytes induced by 10 ng/ml LPS. Granulocytic production of IL-8 induced by 1 ng/ml LPS was significantly (P < 0.05) inhibited by treatment with 1 ug/ml sivelestat, and upregulation of IL-8 by 10 ng/ml LPS was also significantly (P < 0.05) suppressed by 1 and 10 ug/ml sivelestat.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:44:19 GMT 2025` Edited by `admin` on `Wed Apr 02 08:44:19 GMT 2025`
Record UNII	DWI62G0P59
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SIVELESTAT

Official Name

English

LY-544349

Preferred Name

English

SIVELESTAT [USAN]

Common Name

English

ONO-5046

Code

English

SIVELESTAT [MART.]

Common Name

English

sivelestat [INN]

Common Name

English

Sivelestat [WHO-DD]

Common Name

English

LY544349

Code

English

SIVELESTAT [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C783