PF-429242 dihydrochloride (PF429242) is a potent, selective, reversible and competitive inhibitor of proprotein convertase SREBP site 1 protease (S1P, Subtilisin kexin isozyme-1/SKI-1, MBTPS1) with IC50 of 170 nM.
PF-429242 dihydrochloride (PF429242) is a potent, selective, reversible and competitive inhibitor of proprotein convertase SREBP site 1 protease (S1P, Subtilisin kexin isozyme-1/SKI-1, MBTPS1) with IC50 of 170 nM. PF-429242 shows no significant inhibition of trypsin, elastase, proteinase K, plasmin, kallikren, factor XIa, thrombin, or furin at concentrations up to 100 μM and only modest inhibition of urokinase (IC50 = 50 μM) and factor Xa (IC50 = 100 μM). PF-429242 prevented proteolytic processing and nuclear translocation of SREBP (complete inhibition at a dose of 10 μM) in Hep-G2 cells. PF-429242 reduced the expression of key genes involved in cholesterol synthesis (e.g., HMG-CoA synthase; EC50 = 0.3 μM) and fatty acid synthesis (e.g., fatty acid synthase; EC50 = 2 μM) in Hep-G2 cells. PF-429242 (10 and 30 mg/kg/dose i.p.) reduced HMG-CoA synthase gene expression in male CD1 mice. PF-429242 efficiently prevented the processing of glycoprotein (GP) precursor from the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and LASV.
