Nafamostat . mesylate

Background:

Nafamostat mesylate is a cell permeable broad spectrum potent and reversible synthetic serine protease inhibitor and kallikrein inhibitor in vitro and in vivo. It inhibits trypsin (Ki=15nM), tryptase (Ki=95.3pM) and additional proteases in the coagulation cascade including thrombin (Ki=0.84µM). Nafamostat mesylate is a short-acting anticoagulant with anti-inflammatory, anticancer and antiviral properties. As a potential anticancer agent, it blocks canonical NF-κB signaling, targets TNFR1-stimulated cleavage of caspase families and the tryptase of mast cells to improve therapeutic outcome and to ameliorate cancer therapy resistance and avoid immune resistance. It has been shown to reduce eosinophil infiltration, mast cell activation and airway responsiveness in a murine model of asthma. Inhibits the demethylase activity of the fat mass and obesity-associated protein (FTO). As antiviral agent, it inhibits Ebola virus, MERS-CoV and SARS-CoV-2 infection in vitro and potentially the spread of COVID-19. Nafamostat mesylate inhibits TMPRSS2-dependent host cell entry of MERS-CoV. It is also an inhibitor of the enzyme transmembrane serine protease TMPRSS2 and blocks the entry of SARS-CoV-2 (COVID-19) into lung cells in vitro, with roughly 15-fold higher efficiency than Camostat mesylate (Prod. No. AG-CR1-3716), with an EC50 in the low nanomolar range.