PF-429242

PF429242 is a reversible and competitive SREBP site 1 protease (S1P) inhibitor with an IC₅₀ of 175 nM^[1]. In Vitro: 10 μM PF-429242 inhibits endogenous SREBP processing in Chinese hamster ovary cells. PF-429242 also down-regulates the signal from an SRE-luciferase reporter gene in human embryonic kidney 293 cells and the expression of endogenous SREBP target genes in cultured HepG2 cells. In HepG2 cells, PF-429242 inhibits cholesterol synthesis, with an IC₅₀ of 0.5 μM^[1].
The addition of PF-429242 (30 μM) shows statistically significant suppression of infectious viral titers and viral RNA copies in the cell culture fluids. PF-429242 treatment also shows suppressive effects on DENV2 yields in the cultured fluids of human-derived HEK-293, Hep G2, and non-human-primate derived LLC-MK2 cells^[2].
PF-429242 efficiently prevents the processing of GPC from the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and LASV, which correlates with the compound's potent antiviral activity against LCMV and LASV in cultured cells^[3]. In Vivo: In mice treated with PF-429242 for 24 h, the expression of hepatic SREBP target genes is suppressed, and the hepatic rates of cholesterol and fatty acid synthesis are reduced^[1].