Wnt signaling is required for direct multiple biological processes and also plays key roles in the pathogenesis of various diseases. Axin is a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. Axin is a component of the β-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. In Wnt signaling, axin probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B[3].
KY1220 specifically binds to the RGS domain of Axin, activates GSK3β via a conformational change enhancing β-catenin complex assembly, and subsequently degrade both β-catenin and Ras via proteasomal degradation[4]. The inhibitory IC50 of KY1220 on the Wnt/β-catenin pathway was 2.1 μM, and in HEK293 cells, both β-catenin and pan-Ras protein levels were reduced in a dose-dependent manner after treatment with KY1220 at the concentration of 5~50 μM[5]. The proliferation and transformation of HCT15, SW480, D-WT and D-MT colon cancer cells were efficiently inhibited after treatment with KY1220[5].
KY1220 细胞实验
Cell Line
Concentration
Treated Time
Description
References
DLD-1 cells
20 μM
KY1022 inhibited the EMT phenotype in DLD-1 cells
Oncotarget. 2016 Dec 6;7(49):81727-81740
SW480 cells
20 μM
72 hours
KY1022 inhibited the growth of SW480 cells and induced apoptosis
Oncotarget. 2016 Dec 6;7(49):81727-81740
HEK293 cells
20 μM
12 hours
KY1022 increased phosphorylation of β-catenin and Ras via activation of GSK3β, promoting their degradation
Oncotarget. 2016 Dec 6;7(49):81727-81740
LoVo cells
20 μM
18 hours
KY1022 significantly inhibited the migration ability of LoVo cells
Oncotarget. 2016 Dec 6;7(49):81727-81740
KY1220 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
APCMin/+/K-RasG12DLA2 compound mouse model
Intraperitoneal injection
25 mg/kg
Daily for 8 weeks
KY1022 effectively suppressed small intestinal tumor formation and invasion in APCMin/+/K-RasG12DLA2 mice
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