CCT 031374 hydrobromide

An inhibitor of β-catenin/TCF complex signaling

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Background

CCT 031374 hydrobromide is a selective inhibitor of Wnt/β-catenin signaling pathway [1].

The Wnt/β-catenin pathway is activated by the binding of Wnt ligand to a complex comprising LRP5/6 and Frizzled (Fz) receptors and then activates transcription factor/β-catenin-dependent transcription [1].

CCT 031374 hydrobromide is a selective Wnt/β-catenin signaling pathway inhibitor. CCT031374 inhibited BIO-induced β-catenin accumulation in L-cells with IC50 value of 6.1 μM. In HCT116 human colon cancer cell line, CCT031374 inhibited cell proliferation by inducing apoptosis. In mouse L-cells, BIO, a GSK-3 inhibitor, significantly increased total β-catenin levels. While CCT031374 inhibited BIO-induced accumulation of β-catenin in both nuclear and cytosolic. In U2OS GFP-β-catenin human osteosarcoma cells, CCT031374 induced the formation of GFP-β-catenin aggregates. In human neurogenic embryoid bodies, CCT031374 reduced the mRNA levels of endogenous LEF1. Also, CCT031374 inhibited cell growth with GI values of 11.5, 13.9, 13.2, 9.6 and 44 μM in HT29, HCT116, SW480, SNU475 and CCD841Co cancer cell lines, respectively [1].

Reference:
[1].? Ewan K, Pajak B, Stubbs M, et al. A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription. Cancer Res, 2010, 70(14): 5963-5973.