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Identification of nafamostat mesilate as an inhibitor of the fat mass and obesity-associated protein (FTO) demethylase activity.
Chemico-biological Interactions 2018 October 26
Nafamostat mesilate is a serine protease inhibitor and used for the treatment of pancreatitis and cancers. The fat mass and obesity-associated protein (FTO) was identified to be a demethylase and played an important role in physiological processes. The aim of this study was to examine the inhibition of Nafamostat mesilate on FTO demethylase activity. A combination of thermodynamic and enzymatic activity studies provides an insight into the recognition of Nafamostat mesilate by FTO. The binding of Nafamostat mesilate to FTO was driven by higher positive entropy changes and smaller negative enthalpy changes. The structural and thermodynamic information provides the basis for the design of more effective inhibitors for FTO. Our results might provide a novel target protein for Nafamostat mesilate.
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