PF429242 dihydrochloride

PF-429242 is an inhibitor of site-1 protease with an IC₅₀ value of 170 nM for human recombinant site-1 protease.¹ 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.² It also reduces growth of T98G, U87-MG, and A172 glioblastoma cells (IC₅₀s = 0.32, 15.2, and 27.6 μM, respectively).³

1.Hay, B.A., Abrams, B., Zumbrunn, A.Y., et al.Aminopyrrolidineamide inhibitors of site-1 proteaseBioorg. Med. Chem. Lett.17(16)4411-4414(2007) 2.Uchida, L., Urata, S., Ulanday, G.E., et al.Suppressive effects of the site 1 protease (S1P) inhibitor, PF-429242, on Dengue virus propagationViruses8(2)46(2016) 3.Caruana, B.T., Skoric, A., Brown, A.J., et al.Site-1 protease, a novel metabolic target for glioblastomaBiochem. Biophys. Res. Commun.490(3)760-766(2017)