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Details

Stereochemistry ACHIRAL
Molecular Formula C19H17N5O2.2CH4O3S
Molecular Weight 539.582
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NAFAMOSTAT MESYLATE

SMILES

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

InChI

InChIKey=SRXKIZXIRHMPFW-UHFFFAOYSA-N
InChI=1S/C19H17N5O2.2CH4O3S/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;2*1-5(2,3)4/h1-10H,(H3,20,21)(H4,22,23,24);2*1H3,(H,2,3,4)

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
MOL RATIO 2 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C19H17N5O2
Molecular Weight 347.3706
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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 TargetPharmacologyConditionPotency
17.0 nM [IC50]
12.0 µM [IC50]
95.3 pM [Ki]
617.0 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NAFAMOSTAT
Preventing
NAFAMOSTAT

Cmax

ValueDoseCo-administeredAnalytePopulation
16.4 ng/mL
10 mg single, intravenous
NAFAMOSTAT blood
Homo sapiens
61.5 ng/mL
20 mg single, intravenous
NAFAMOSTAT blood
Homo sapiens
93.2 ng/mL
40 mg single, intravenous
NAFAMOSTAT blood
Homo sapiens
14.49 ng/mL
10 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens
40.4 ng/mL
20 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens
60.43 ng/mL
40 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1655.84 ng × min/mL
10 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens
3571.14 ng × min/mL
20 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens
6880.46 ng × min/mL
40 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
23.1 min
40 mg single, intravenous
NAFAMOSTAT blood
Homo sapiens
112.42 min
10 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens
128.19 min
20 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens
122.91 min
40 mg single, intravenous
NAFAMOSTAT plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
33.36%
NAFAMOSTAT serum
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as victim

PubMed

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
Record UNII
1D2T74921W
Record Status Validated (UNII)
Record Version