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IWR-1, also known as IWR-1-endo, is a an inhibitor of the Wnt signaling cascade through inhibiting TNKSs, binding only to the adenosine-binding site. IWR-1 inhibits epithelial-mesenchymal transition of colorectal cancer cells through suppressing Wnt/β-catenin signaling as well as survivin expression. IWR-1 inhibits cell proliferation and EMT even in the presence of TNF-α-induced cancer cell stimulation. IWR-1 also significantly suppressed cell migration, invasion, and matrix metalloproteinase activities of CRC cell lines. IWR-1 provides EMT reversal effects by directly suppressing survivin expression.