PF-429242 is an inhibitor of site-1 protease with an IC50 value of 170 nM for human recombinant site-1 protease. It is selective for site-1 protease over trypsin, elastase, proteinase K, plasmin, kallikren, factor XIa, thrombin, and furin at concentrations up to 100 μM. PF-429242 completely inhibits proteolytic processing and nuclear translocation of sterol regulatory element-binding protein (SREBP) in HepG2 cells at a concentration of 10 μM. It also reduces expression of HMG-CoA synthase and fatty acid synthase (EC50s = 0.3 and 2 μM, respectively) and inhibits cholesterol synthesis (EC50 = 600 nM) in HepG2 cells and reduces cholesterol and fatty acid synthesis in CD-1 mice. PF-429242 inhibits replication of dengue virus serotypes 1-4 in infected HeLa cells. It also reduces growth of T98G, U87-MG, and A172 glioblastoma cells (IC50s = 0.32, 15.2, and 27.6 μM, respectively).
