The effects of FUT-175 (nafamostat mesilate) on blood coagulation and experimental disseminated intravascular coagulation(DIC).

Koshiyama, Yoshiko; Kobori, Akemi; Ogihara, Madoka; Yokomoto, Yasuki; Ohtani, Kyoko; Shimamura, Kazunori; Iwaki, Masahiro

doi:10.1254/fpj.90.313

Cited by 7 publications

(6 citation statements)

References 1 publication

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“…Experimentally, NM reduces the mortality of the endotoxin-induced DIC in rats (Yoshikawa et al 1983;Koshiyama et al 1987), and also improves DIC caused by circulatory arrest in dogs (Takemoto et al 1986). And NM inhibits kallikrein ) and the factor VIIa complex (Uchiba et al 1994), one of proteases associated with the pathogenesis of DIC, and has other anti-coagulant effects (Hitomi et al 1985).…”

Section: Management Of Dic In Evdmentioning

confidence: 98%

“…In addition, NM improved DIC in the experimental animal models (Yoshikawa et al 1983;Koshiyama et al 1987), and had anticoagulant effects in vitro (Uchiba et al 1994) and in humans Hitomi et al 1985). In this connection, NM has been used for the treatment of DIC (Shibata et al 1988;Okamoto et al 1991), as well as for extracorporeal circulation (Tsukagoshi et al 2000) and hemodialysis (Pak et al 1988) Such off-label use of the drug has advantages over developing a new drug in terms of saving the time until application to humans and of the logistics: the clinical use of an already approved drug for symptomatic treatment would not be associated with any major ethical problems, although there may have some restrictions.…”

Section: Introductionmentioning

confidence: 97%

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A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease

Nishimura

Yamaya

2015

Tohoku J. Exp. Med.

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Ebola virus disease (EVD) has been a great concern worldwide because of its high mortality. EVD usually manifests with fever, diarrhea and vomiting, as well as disseminated intravascular coagulation (DIC). To date, there is neither a licensed Ebola vaccine nor a promising therapeutic agent, although clinical trials are ongoing. For replication inside the cell, Ebola virus (EBOV) must undergo the proteolytic processing of its surface glycoprotein in the endosome by proteases including cathepsin B (CatB), followed by the fusion of the viral membrane and host endosome. Thus, the proteases have been considered as potential targets for drugs against EVD. However, no protease inhibitor has been presented as effective clinical drug against it. A synthetic serine protease inhibitor, nafamostat mesilate (NM), reduced the release of CatB from the rat pancreas. Furthermore, it has anticoagulant activities, such as inhibition of the factor VIIa complex, and has been used for treating DIC in Japan. Thus, NM could be considered as a drug candidate for the treatment of DIC induced by EBOV infection, as well as for the possible CatB-related antiviral action. Moreover, the drug has a history of large-scale production and clinical use, and the issues of safety and logistics might have been cleared. We advocate in vitro and in vivo experiments using active EBOV to examine the activities of NM against the infection and the DIC induced by the infection. In addition, we suggest trials for comparison among anti-DIC drugs including the NM in EVD patients, in parallel with the experiments.

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Section: Management Of Dic In Evdmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease

Nishimura

Yamaya

2015

Tohoku J. Exp. Med.

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“…46 FUT 175, chemically amidinonaphthyl-guanidinobenzoate, a rather nonselective proteinase inhibitor, is also proposed for anticoagulant and antithrombotic use. [47][48][49] The developments just mentioned show that several groups are going beyond the synthetic and biochemical work in this field and are evaluating the potential of various types of thrombin inhibitors as anticoagulant agents in vitro and in vivo.…”

Section: Fig 1 Structures Of Prototype Compounds Of the Arginine Dementioning

confidence: 99%

Pharmacologic Aspects of the Development of Selective Synthetic Thrombin Inhibitors as Anticoagulants

Hauptmann

Markwardt²

1992

Semin Thromb Hemost

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“…Nafamostat mesylate (benzoic acid, 4-[(aminoiminomethyl) amino]-, 6-(aminoimino-methyl)-2-naphthalenyl ester, dimethanesulfonate; CAS: 82956-11-4, Fig. 1 ) is a serine protease inhibitor used in the treatment of acute pancreatitis and disseminated intravascular coagulation [ [1] , [2] , [3] , [4] , [5] , [6] ]. It can effectively prevent post-endoscopic retrograde cholangiopancreatography pancreatitis [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of impurities in nafamostat mesylate using HPLC-IT-TOF/MS: A series of double-charged ions

Zhang

An²,

Zhang

et al. 2020

Journal of Pharmaceutical Analysis

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Nafamostat mesylate is a serine protease inhibitor used in the treatment of acute pancreatitis. The impurities in nafamostat mesylate, the active pharmaceutical ingredient (API), were profiled via high performance liquid chromatography tandem ion trap coupled with time-of-flight mass spectrometer (HPLC-IT-TOF/MS). The chromatography was performed on an ACE-3 C 18 column (200 mm × 4.6 mm, 3 μm) using methanol and 0.1% formic acid in purified water as mobile phase at a flow rate of 1.0 mL/min. The ions were detected by IT-TOF/MS with a full-scan mass analysis from m/z 100 to 800. In total, eleven impurities were detected in nafamostat mesylate API. The impurity profile was estimated based on the HPLC-IT-TOF/MS data, including accurate masses, MS n fingerprints of fragmentation pathways and a series of double-charged ions. Finally, seven impurities were identified and reported for the first time. The results will provide technical support for the quality control and clinical safety of nafamostat mesylate.

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The effects of FUT-175 (nafamostat mesilate) on blood coagulation and experimental disseminated intravascular coagulation(DIC).

Cited by 7 publications

References 1 publication

A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease

A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease

Pharmacologic Aspects of the Development of Selective Synthetic Thrombin Inhibitors as Anticoagulants

Identification of impurities in nafamostat mesylate using HPLC-IT-TOF/MS: A series of double-charged ions

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