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PKF118-310 is an inhibitor of the interaction between T cell factor 4 (Tcf4) and β-catenin that is produced by Actinomycete strains. It disrupts binding of β-catenin to a GST-Tcf4 fusion protein in HCT116 cell lysates (IC50 = 0.8 uM). PKF118-310 blocks appearance of the Tcf4 and β-catenin complex bound to DNA in an EMSA assay. It reduces levels of the β-catenin regulated proteins c-Myc and cyclin D1 but has no effect on cyclin E in HCT116 cells. PKF118-310 (0.5 pmol) abrogates β-catenin, but not siamois, ventral body axis duplication induced by mRNA in Xenopus embryos. It reduces growth of HCT116, HT-29, PC3, and DU145 cancer cells in vitro (IC50s = 170-300 nM). PKF118-310 (1 mg/kg twice per week) reduces tumor growth and expression of c-Myc, cyclin D1, and Survivin in a HepG2 mouse xenograft model.

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