Nafamostat mesylate
[CAS# 82956-11-4]

Identification

• Classification: Biochemical >> Inhibitor >> Proteases >> Serine protease inhibitor
• Name: Nafamostat mesylate
• Synonyms: 6-Amidino-2-naphthyl 4-guanidino-benzoate dimethanesulphonate
• Molecular Formula: C₁₉H₁₇N₅O₂.2(CH₄O₃S);C₂₁H₂₅N₅O₈S₂
• Molecular Weight: 539.58
• CAS Registry Number: 82956-11-4
• EC Number: 692-168-2
• SMILES: CS(=O)(=O)O.CS(=O)(=O)O.C1=CC(=CC=C1C(=O)OC2=CC3=C(C=C2)C=C(C=C3)C(=N)N)N=C(N)N

Properties

• Solubility: 53 mg/mL (water), 20 mg/mL (DMSO) (Expl.)
• Melting point: 259-261 °C (Expl.)

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H361
• Safety Statements: P203-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

Nafamostat mesylate is a synthetic chemical compound primarily used as an anticoagulant and an antiviral agent. It belongs to a class of protease inhibitors, which are known for their ability to inhibit various enzymes that play a role in blood clotting and viral replication. Nafamostat mesylate was first synthesized in the 1980s by researchers looking for potent agents to treat thrombotic disorders and viral infections. Its discovery was part of ongoing efforts to develop more effective drugs for managing conditions like disseminated intravascular coagulation (DIC) and for treating certain viral infections, including those caused by hepatitis B and C.

The synthesis of nafamostat mesylate involves a complex series of chemical reactions that introduce a mesylate group to the nafamostat molecule. This mesylate ester group enhances the solubility and bioavailability of the compound, making it more effective when administered. Nafamostat mesylate functions by inhibiting various enzymes, including thrombin and other serine proteases, which are critical in the coagulation cascade. By blocking these enzymes, nafamostat mesylate helps prevent the formation of abnormal blood clots, thus managing bleeding disorders and improving blood circulation in patients with clotting conditions.

One of the most significant applications of nafamostat mesylate is in the treatment of acute pancreatitis, particularly when it is complicated by DIC. In these conditions, nafamostat mesylate works by regulating the coagulation system, thus preventing further complications. It has also been used in certain liver diseases, where its antiviral properties help reduce the replication of viruses such as hepatitis B and C. Nafamostat mesylate is sometimes used off-label in the management of conditions like COVID-19, as its protease inhibition may help reduce viral replication, though its use for this purpose is still under investigation.

In addition to its role in treating blood clotting and viral infections, nafamostat mesylate is being explored for its potential use in cancer therapy. Studies have shown that its protease-inhibiting properties could be valuable in inhibiting the spread of cancerous cells, though clinical evidence for this application is still limited. The compound is administered through intravenous injection, and its use requires careful monitoring due to its potent effects on the coagulation system.

In conclusion, nafamostat mesylate is a versatile drug with significant therapeutic potential. Its ability to inhibit proteases that are involved in both coagulation and viral replication has made it an important agent in the treatment of several medical conditions. As research into its applications continues, nafamostat mesylate may find new uses in the management of various diseases, particularly those that involve abnormal blood clotting or viral infections.

References

2019. Nafamostat and sepimostat identified as novel neuroprotective agents via NR2B N-methyl-D-aspartate receptor antagonism using a rat retinal excitotoxicity model. Scientific Reports, 9(1).
DOI: 10.1038/s41598-019-56905-x

1984. Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments. Japanese Journal of Pharmacology, 35(3).
DOI: 10.1254/jjp.35.203

1993. The therapeutic effect of a new synthetic protease inhibitor (E-3123) on hemodynamic changes during experimental acute pancreatitis in dogs. Journal of Gastroenterology, 28(2).
DOI: 10.1007/bf02775005