PPAR
Wnt
β-catenin
FH535 is an inhibitor of Wnt/β-catenin and PPAR. FH535 inhibits PPARγ and PPARδ transactivation in HCT116 cells. FH535 (15 μM) activities depend on functional PPARδ but does not require a cysteine residue in the PPAR ligand-binding domain. FH535 inhibits recruitment of the coactivators GRIP1 and β-catenin to PPARδ and PPARγ. FH535 shows toxic effects on 12 carcinoma cell lines expressing wnt/β-catenin pathway. FH535 (20 μM) suppresses the β-catenin pathway in pancreatic cancer cells, and inhibits pancreatic cancer cell migration. Furthermore, FH535 (20, 40 μM) inhibits pancreatic cancer cell invasion and cell growth. FH535 represses angiogenesis-related genes in pancreatic cancer cells.
FH535 (25 mg/kg, i.p.) exhibits an anti-tumor effect on pancreatic cancer xenografts in mice. FH535 also represses angiogenesis in pancreatic cancer xenografts.