U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H17N5O2
Molecular Weight 347.3713
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NAFAMOSTAT

SMILES

c1cc(cc2ccc(cc12)OC(=O)c3ccc(cc3)NC(=N)N)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
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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.
Preventing
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

PubMed

TitleDatePubMed
A serine protease inhibitor, nafamostat mesilate, suppresses aldosterone secretions in vivo.
2004 Dec
A case of heparin-induced thrombocytopenia with sepsis and congestive heart failure--first autopsy report on Japan--.
2004 Dec
[Pregnancy and delivery in patients with hemodialysis].
2004 Jun
[Heparin-induced thrombocytopenia in patients on hemodialysis].
2004 Jun
[Treatment of uremic patients with high bleeding risk].
2004 Jun
[Blood purification for patients with chronic renal failure accompanied by severe liver disease].
2004 Jun
Effects of anti-inflammatory cytokine agent (FR167653) and serine protease inhibitor on warm ischemia-reperfusion injury of the liver graft.
2004 May 27
[Continuous regional arterial infusion of protease inhibitor and antibiotic for severe acute pancreatitis].
2004 Nov
[Treatment of acute pancreatitis with protease inhibitor, H2 receptor antagonist and somatostatin analogue].
2004 Nov
Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion.
2004 Nov
Continuous hemodiafiltration in pediatric critical care patients.
2004 Oct
[Role of pancreatic enzymes in gut injury secondary to trauma/hemorrhagic shock in rats].
2004 Oct
Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts.
2004 Sep
Nafamostat preserves neutrophil deformability and reduces microaggregate formation during simulated extracorporeal circulation.
2005 Apr
Correlation between serum nafamostat mesilate and activated coagulation time during continuous hemodiafiltration.
2005 Apr
Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis.
2005 Apr
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
Mast cell tryptase stimulates DLD-1 carcinoma through prostaglandin- and MAP kinase-dependent manners.
2005 Aug
Nafamostat mesilate induces production of interleukin-12 and -18 in human peripheral blood mononuclear cells.
2005 Aug
Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation.
2005 Aug
[A patient with Vibrio vulnificus meningoencephalitis].
2005 Jan
Physiology and pathophysiology of proteinase-activated receptors (PARs): role of tryptase/PAR-2 in vascular endothelial barrier function.
2005 Jan
Open heart surgery in a patient with paroxysmal nocturnal hemoglobinuria.
2005 Jun
Involvement of neutrophil recruitment and protease-activated receptor 2 activation in the induction of IL-18 in mice.
2005 Nov
JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis.
2006
Involvement of human blood arylesterases and liver microsomal carboxylesterases in nafamostat hydrolysis.
2006 Apr
Nafamostat attenuated the impairment of fibrinolysis in animal sepsis model by suppressing the increase of plasminogen activator inhibitor type 1.
2006 Apr
Anti-tryptase treatment using nafamostat mesilate has a therapeutic effect on experimental colitis.
2006 Aug
Implantation Serine Proteinases heterodimerize and are critical in hatching and implantation.
2006 Dec 11
Leukocytapheresis for ulcerative colitis: a comparative study of anticoagulant (nafamostat mesilate vs. dalteparin sodium) for reducing clinical complications.
2006 Feb
[Quality of life in surgical treatment of pancreatic cancer].
2006 Jan
Myeloperoxidase as a marker of hemodialysis biocompatibility and oxidative stress: the underestimated modifying effects of heparin.
2006 Jan
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
The role of a protease inhibitor against hepatectomy.
2006 Jan-Feb
[Prostasin].
2006 Jul
Serine protease inhibitors nafamostat mesilate and gabexate mesilate attenuate allergen-induced airway inflammation and eosinophilia in a murine model of asthma.
2006 Jul
Anticoagulation and continuous renal replacement therapy.
2006 Jul-Aug
Topical application of epidermal growth factor accelerates wound healing by myofibroblast proliferation and collagen synthesis in rat.
2006 Jun
Human complement-activating immunoglobulin (Ig)G3 antibodies are essential for porcine endothelial cell activation.
2006 May
[Postoperative acute pulmonary thromboembolism treated with nafamostat mesilate].
2006 May
Complement activation is involved in biological responses to leukocyte adsorptive apheresis.
2006 May
Properties of poly(lactic-co-glycolic acid) nanospheres containing protease inhibitors: camostat mesilate and nafamostat mesilate.
2006 May 11
Effects of nafamostat mesilate on ADP-induced platelet aggregation and disaggregation in hemodialysis patients.
2006 May-Jun
Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: possible involvement of CD14 and TLR-4 downregulation on Kupffer cells.
2006 Nov
Nafamostat mesilate inhibits high-mobility group box 1 by lipopolysaccharide stimulation in murine macrophage RAW 264.7.
2007 Apr
Antitumor effects of Nafamostat mesilate on head and neck squamous cell carcinoma.
2007 Dec
[Anticoagulation of extracorporeal circuit in critically ill patients].
2007 Jan-Feb
Pancreatic enzymes generate cytotoxic mediators in the intestine.
2007 Mar
Low-volume continuous hemodiafiltration with nafamostat mesilate increases trypsin clearance without decreasing plasma trypsin concentration in severe acute pancreatitis.
2007 Mar-Apr
Mechanisms of synthetic serine protease inhibitor (FUT-175)-mediated cell death.
2007 May 15
Patents

Sample Use Guides

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.
Name Type Language
NAFAMOSTAT
INN   MI   WHO-DD  
INN  
Official Name English
BENZOIC ACID, 4-((AMINOIMINOMETHYL)AMINO)-, 6-(AMINOIMINOMETHYL)-2-NAPHTHALENYL ESTER
Common Name English
NAFAMOSTAT [INN]
Common Name English
NAFAMOSTAT [WHO-DD]
Common Name English
NAFAMOSTAT [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
NCI_THESAURUS C257
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
FDA ORPHAN DRUG 742120
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL273264
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
EPA CompTox
81525-10-2
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
PUBCHEM
4413
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
DRUG BANK
DB12598
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
EVMPD
SUB09114MIG
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
FDA UNII
Y25LQ0H97D
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
CAS
81525-10-2
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
DRUG CENTRAL
1867
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
MERCK INDEX
M7704
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
NAFAMOSTAT
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
IUPHAR
4262
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
INN
5682
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
MESH
C032855
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY
NCI_THESAURUS
C96292
Created by admin on Sat Jun 26 07:56:38 UTC 2021 , Edited by admin on Sat Jun 26 07:56:38 UTC 2021
PRIMARY