KY1220 destabilizes both β-catenin and Ras by targeting the Wnt/β-catenin pathway. It has an IC50 of 2.1 μM in HEK293 reporter cells.

KY1220 accelerates the degradation rates of both β-catenin and Ras in SW480 cell lines. KY1220 dose-dependently reduces Wnt3a-CM-induced TOPflash reporter activation and mRNA expression of Wnt target genes CCND1 and MYC in HEK293 cells. Ras destabilization by KY1220 consequently inhibits the activities of both ERK and Akt, which are downstream effectors of Ras in SW480 cells harboring a KRAS mutation. In HEK293 cells, both β-catenin and pan-Ras protein levels are similarly reduced in a dose-dependent manner after treatment with KY1220, whereas the mRNA levels of CTNNB1 (which encodes β-catenin), NRAS, KRAS, and HRAS remain unchanged. K-Ras, which has a critical role in the progression of CRCs, is also destabilized by KY1220 via polyubiquitin-dependent proteasomal degradation. The proliferation and transformation of the HCT15, SW480, D-WT, and D-MT CRC cells are efficiently inhibited after treatment with KY1220.