PKF118-310 (CAS 84-82-2)

PKF118-310 is an inhibitor of survivin expression and antagonist of Tcf4/b-catenin signaling. Shown to induce apoptosis in tumor cells.PKF118-310, a product of Actinomycete strains, functions as an inhibitor for the protein-protein interaction between T cell factor 4 (Tcf4) and β-catenin. In HCT116 cell lysates, it disrupts the binding of β-catenin to a GST-Tcf4 fusion protein with an IC50 of 0.8 µM. Moreover, PKF118-310 blocks the appearance of the Tcf4 and β-catenin complex bound to DNA, as observed in an EMSA assay. This inhibitor reduces the levels of β-catenin regulated proteins c-Myc and cyclin D1 in HCT116 cells, while having no impact on cyclin E. Additionally, in Xenopus embryos, PKF118-310 (at 0.5 pmol) prevents β-catenin (but not siamois) induced ventral body axis duplication caused by mRNA. In vitro studies show that PKF118-310 curtails the growth of various cancer cells, such as HCT116, HT-29, PC3, and DU145, with IC50 values ranging from 170 to 300 nM. Notably, in a HepG2 mouse xenograft model, a dose of 1 mg/kg twice per week reduces tumor growth while also downregulating the expression of c-Myc, cyclin D1, and Survivin.