NAFAMOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17N5O2
Molecular Weight	347.3706
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=N)NC1=CC=C(C=C1)C(=O)OC2=CC3=C(C=C2)C=C(C=C3)C(N)=N

InChI

InChIKey=MQQNFDZXWVTQEH-UHFFFAOYSA-N

InChI=1S/C19H17N5O2/c20-17(21)14-2-1-13-10-16(8-5-12(13)9-14)26-18(25)11-3-6-15(7-4-11)24-19(22)23/h1-10H,(H3,20,21)(H4,22,23,24)

HIDE SMILES / InChI

Molecular Formula	C19H17N5O2
Molecular Weight	347.3706
Charge	0
Count

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

Description
Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=35600 | https://www.ncbi.nlm.nih.gov/pubmed/8713783 | https://www.ncbi.nlm.nih.gov/pubmed/8029816

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. Nafamostat is approved and marketed in Japan. It relieves symptoms such as pain due to inflammation of the spleen. It improves visceral disorders and bleeding tendency caused by blood clotting tendency in the vessels. It prevents coagulation in the blood circuit during hemodialysis. It is usually used to improve acute symptoms of pancreatitis (acute pancreatitis, acute exacerbation phase of chronic pancreatitis, post-operative acute pancreatitis, acute pancreatitis after pancreatography, traumatic pancreatitis) and to prevent disseminated intravascular coagulation (DIC) and clotting of perfusing blood in extracorporeal blood circuit. Nafamostat mesilate significantly inhibits the release of platelet beta-thromboglobulin (beta TG) at 60 and 120 min. Nafamostat mesilate (NM) prevents any significant release of neutrophil elastase; at 120 min, plasma elastase-alpha 1-antitrypsin complex is 0.16 mg/mL in the NM group and 1.24 mg/mL in the control group. Nafamostat mesilate completely inhibits formation of complexes of C1 inhibitor with kallikrein and FXIIa.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Trypsin I 2 Target ID: CHEMBL209 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10206542 \| https://www.ncbi.nlm.nih.gov/pubmed/9544206	Inhibitor 8297	17.0 nM [IC50]
Complement C1r 2 Target ID: CHEMBL4611 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10206542 \| https://www.ncbi.nlm.nih.gov/pubmed/9544206	Inhibitor 8297	12.0 µM [IC50]
Tryptase beta-1 2 Target ID: CHEMBL2617 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12939527	Inhibitor 8297	95.3 pM [Ki]
Transient receptor potential cation channel subfamily M member 7 6 Target ID: CHEMBL1250412 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21122141	Inhibitor 8297	617.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pancreatitis 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25822153 https://www.ncbi.nlm.nih.gov/pubmed/21206331	Primary		Approved 8429	NAFAMOSTAT Approved Use This medicine relieves symptoms such as pain due to inflammation of the spleen. It improves visceral disorders and bleeding tendency caused by blood clotting tendency in the vessels. It prevents coagulation in the blood circuit during hemodialysis. It is usually used to improve acute symptoms of pancreatitis (acute pancreatitis, acute exacerbation phase of chronic pancreatitis, post-operative acute pancreatitis, acute pancreatitis after pancreatography, traumatic pancreatitis) and to prevent disseminated intravascular coagulation (DIC) and clotting of perfusing blood in extracorporeal blood circuit.
Disseminated intravascular coagulation 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26466700 https://www.ncbi.nlm.nih.gov/pubmed/11372771	Preventing		Approved 8429	NAFAMOSTAT Approved Use This medicine relieves symptoms such as pain due to inflammation of the spleen. It improves visceral disorders and bleeding tendency caused by blood clotting tendency in the vessels. It prevents coagulation in the blood circuit during hemodialysis. It is usually used to improve acute symptoms of pancreatitis (acute pancreatitis, acute exacerbation phase of chronic pancreatitis, post-operative acute pancreatitis, acute pancreatitis after pancreatography, traumatic pancreatitis) and to prevent disseminated intravascular coagulation (DIC) and clotting of perfusing blood in extracorporeal blood circuit.

PubMed

Title	Date	PubMed
A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate.	1999 Sep	10655909
Benefit of continuous regional arterial infusion of protease inhibitor and antibiotic in the management of acute necrotizing pancreatitis.	2001	12120252
[Perioperative management for radical esophagectomy in a patient with polycythemia vera].	2001 Dec	11797364
[A case of pancreatic ascites due to rupture of pancreatic pseudocyst successfully treated with continuous arterial infusion of nafamostat mesilate].	2001 Nov	11729660
Granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid.	2001 Sep	11604554
Induction of IkappaB-kinase by cholecystokinin is mediated by trypsinogen activation in rat pancreatic lobules.	2002	12592100
Severe abdominal pain associated with allergic reaction to nafamostat mesilate in a chronic hemodialysis patient.	2002 Oct	12413011
Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells.	2003 Aug	12781870
Reduction of oxidative stress augments natriuretic effect of furosemide in moderate heart failure.	2003 Jan	12514674
Inhibition of prostasin secretion by serine protease inhibitors in the kidney.	2003 Jan	12506133
A potent tryptase inhibitor nafamostat mesilate dramatically suppressed pulmonary dysfunction induced in rats by a radiographic contrast medium.	2003 Mar	12642398
Nafamostat mesilate suppresses NF-kappaB activation and NO overproduction in LPS-treated macrophages.	2003 Sep	12890431
A serine protease inhibitor, nafamostat mesilate, suppresses aldosterone secretions in vivo.	2004 Dec	15894839
A case of heparin-induced thrombocytopenia with sepsis and congestive heart failure--first autopsy report on Japan--.	2004 Dec	15564710
Effects of nafamostat mesilate and minimal-dose aprotinin on blood-foreign surface interactions in cardiopulmonary bypass.	2004 Feb	14759453
Transporter-mediated renal handling of nafamostat mesilate.	2004 Feb	14705184
[Anticoagulant].	2004 May	15197947
[How to use anticoagulants in hemodialysis therapy].	2004 May	15197908
Correlation between serum nafamostat mesilate and activated coagulation time during continuous hemodiafiltration.	2005 Apr	15787634
Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis.	2005 Apr	15782103
Small volume resuscitation with hypertonic saline is more effective in ameliorating trauma-hemorrhagic shock-induced lung injury, neutrophil activation and red blood cell dysfunction than pancreatitic protease inhibition.	2005 Aug	16294064
Nafamostat attenuated the impairment of fibrinolysis in animal sepsis model by suppressing the increase of plasminogen activator inhibitor type 1.	2006 Apr	16612309
Anti-tryptase treatment using nafamostat mesilate has a therapeutic effect on experimental colitis.	2006 Aug	16803693
Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice.	2006 Jan 13	16359660
[Prostasin].	2006 Jul	16895180
[Postoperative acute pulmonary thromboembolism treated with nafamostat mesilate].	2006 May	16715921
Antitumor effects of Nafamostat mesilate on head and neck squamous cell carcinoma.	2007 Dec	17337140

Patents

Sample Use Guides

In Vivo Use Guide

Acute Kidney Injury: Initial dose of nafamostat mesilate is 20mg/hr. Dosage is adjusted from 10mg to 30mg/hr according to patients' status. For priming, two vial of nafamostat mesilate was dissolved in 2mL of 5% glucose fluid, and then mixed with 1000mL of normal saline. After carefully removing air bubble from the circuit with the prepared fluid, nafamostat mesilate was dissolved with 15 mL of 5% glucose fluid and loaded in anticoagulation line with starting dose of 20mg/hr.

Route of Administration: Intravenous

In Vitro Use Guide

Nafamostat inhibited extrinsic pathway activity (TF-F.VIIa mediated-F.Xa generation) in a concentration dependent manner; the IC50 was 1.0 x 10(-7) M. Nafamostat inhibited TF-F.VIIa complex activity with an IC50 of 1.5 x 10(-7) M.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:52:03 GMT 2023` Edited by `admin` on `Fri Dec 15 15:52:03 GMT 2023`
Record UNII	Y25LQ0H97D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NAFAMOSTAT

Official Name

English

Nafamostat [WHO-DD]

Common Name

English

BENZOIC ACID, 4-((AMINOIMINOMETHYL)AMINO)-, 6-(AMINOIMINOMETHYL)-2-NAPHTHALENYL ESTER

Common Name

English

nafamostat [INN]

Common Name

English

NAFAMOSTAT [MI]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

835721