KY1220

292168-79-7

C14H10N4O3S

DMSO : >= 100 mg/mL (318.15 mM)

Stem Cell/Wnt; Stem Cell/Wnt

KY1220 is a compound that destabilizes both beta-catenin and Ras, via targeting the Wnt/beta-catenin pathway; with an IC₅₀ of 2.1 uM in HEK293 reporter cells. IC50 & Target: IC50: 2.1 uM (HEK293 reporter cells)^[1] In Vitro: KY1220 shows an IC₅₀ of 2.1 uM in HEK293 reporter cells. KY1220 dose dependently decreases Wnt3a-CM-induced TOPflash reporter activation and mRNA expression of Wnt target genes CCND1 and MYC in HEK293 cells. In HEK293 cells, both beta-catenin and panRas protein levels are similarly reduced in a dose-dependent manner after treatment with KY1220, whereas the mRNA levels of CTNNB1 (which encodes beta-catenin), NRAS, KRAS and HRAS remain unchanged. K-Ras, which has a critical role in progression of CRCs, is also destabilized by KY1220 via polyubiquitin-dependent proteasomal degradation. KY1220 accelerates the degradation rates of both beta-catenin and Ras in SW480 cell lines. 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. The proliferation and transformation of the HCT15, SW480, D-WT and D-MT CRC cells are efficiently inhibited after treatment with KY1220^[1].