Nafamostat Mesylate is a synthetic serine protease inhibitor, inhibiting a number of Lys/Arg-specifc serine proteinases. It is a tryptase inhibitor. It is an anticoagulant. proventing the proteolysis of fibrinogen into fibrin. The compound has anti-viral, anti-inflammatory, and anti-cancer properties.
Nafamostat Mesylate has potential for COVID-19 research as it has potent in vitro anti-viral inhibitor in lung cells. A number of phase 2 and 3 clinical trials are underway in several countries.
| Mechanism of Action | Anti-viral activity is via inhibition of serine protease, which is required for the host membrane fusion of viral envelope protein. Its anti-inflammatory properties are to to the significantly inhibition of the release of platelet beta-thromboglobulin. |
Spectrum |
Anti-viral activity against MERS-CoV, influenza virus, and SARS-CoV-2. Also effective against obligate intracellular bacterium Chlamydia trachomatis. |
| Microbiology Applications | During in vitro studies, the compound is effective with MERS-CoV, influenza virus, and SARS-CoV-2. A quantitative fusion assay dependent on SARS-CoV-2 S protein, angiotensin I convertin enzyme 2 (ACE2 and TMPRSS2, and found that the compound inhibitied the fusion. Nafamostat Mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM in a cell-type-dependent manner (Yamamoto et al, 2020). |
| Eukaryotic Cell Culture Applications | Nafamostat Mesylate inhibits chlamydial intracellular growth in cell culture and reduced both the inclusion size and number in cell culture. Nafamostat mesylate mainly inhibits reticulate body replication (Peng et al, 2020). |
| Cancer Research Applications | Nafamostat Mesilate inhibited NF-kappaB activation and induced apoptosis of pancreatic cancer cells and was examined by electrophoretic mobility shift assay (in vitro). The compound suppressed pancreatic tumor growth (Uwagawa et al, 2009). |
| Molecular Formula | C19H17N5O2 · 2CH4O3S |
| References |
Hoffmann M et al (2020) Nafamostat Mesylate blocks activation of SARS-CoV-2: New treatment option for COVID-19. Antimicrob. Agents Chemother. 64(6):e00754-20 Homma S (2018) Nafamostat mesilate, a serine protease inhibitor, suppresses interferon-gamma-induced up-regulation of programmed cell death ligand 1 in human cancer cells. Int. Immunopharmacol. 54:39-45 PMID 29100036 Peng L et al (2020) Nafamostat mesylate inhibits chlamydial intracellular growth in cell culture and reduces chlamydial infection in the mouse genital tract. Microbial Pathogenesis,147:104413 Sundaram S et al (1996) Nafamostat Mesilate, a broad-spectrum protease inhibitor, modulates platelet, neutrophil and contact activation in simulated extracorporeal circulation. Thromb Haemost. 175(1):76-82. PMID 8713783 Uwagawa T et al (2009) Combination chemotherapy of Nafamostat Mesilate with gemcitabine for pancreatic cancer targeting NF-kappaB activation. Anticancer Res.29(8):3173-3178 PMID 19661331 |
