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
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)
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 | Condition | Potency |
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Target ID: CHEMBL209 |
17.0 nM [IC50] | ||
Target ID: CHEMBL4611 |
12.0 µM [IC50] | ||
Target ID: CHEMBL2617 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12939527 |
95.3 pM [Ki] | ||
Target ID: CHEMBL1250412 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21122141 |
617.0 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | NAFAMOSTAT Approved UseThis 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. |
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Preventing | NAFAMOSTAT Approved UseThis 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 |
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Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease. | 1992 Nov |
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Successful treatment of severe acute pancreatitis by the combination therapy of continuous arterial infusion of a protease inhibitor and continuous hemofiltration. | 2001 Aug |
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[Anti-bleeding effect of nafamostat mesilate for the surgery of thoracic ascending aorta]. | 2001 Aug |
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Regional effects of nafamostat, a novel potent protease and complement inhibitor, on severe necrotizing pancreatitis. | 2001 Aug |
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Broad-spectrum and selective serine protease inhibitors prevent expression of platelet-derived growth factor-BB and cerebral vasospasm after subarachnoid hemorrhage: vasospasm caused by cisternal injection of recombinant platelet-derived growth factor-BB. | 2001 Jul |
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Induction of IkappaB-kinase by cholecystokinin is mediated by trypsinogen activation in rat pancreatic lobules. | 2002 |
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Changes in blood viscosity with synthetic protease inhibitors. | 2003 Apr |
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Reduction of oxidative stress augments natriuretic effect of furosemide in moderate heart failure. | 2003 Jan |
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Inhibition of enteral enzymes by enteroclysis with nafamostat mesilate reduces neutrophil activation and transfusion requirements after hemorrhagic shock. | 2004 Mar |
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Correlation between serum nafamostat mesilate and activated coagulation time during continuous hemodiafiltration. | 2005 Apr |
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Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis. | 2005 Apr |
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Mast cell tryptase stimulates DLD-1 carcinoma through prostaglandin- and MAP kinase-dependent manners. | 2005 Aug |
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Open heart surgery in a patient with paroxysmal nocturnal hemoglobinuria. | 2005 Jun |
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Antitumor effects of Nafamostat mesilate on head and neck squamous cell carcinoma. | 2007 Dec |
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[Anticoagulation of extracorporeal circuit in critically ill patients]. | 2007 Jan-Feb |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01761994
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8029816
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.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
835721
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NCI_THESAURUS |
C783
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NCI_THESAURUS |
C257
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FDA ORPHAN DRUG |
742120
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CHEMBL273264
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DTXSID0048420
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4413
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DB12598
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SUB09114MIG
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100000091465
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Y25LQ0H97D
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81525-10-2
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1867
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m7704
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NAFAMOSTAT
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4262
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5682
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C032855
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C96292
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)