KYA1797K is a highly potent and selective inhibitor. Wnt/β-catenin IC50 is 0.75 μM through TOPflash assay.

Wnt/β-catenin:0.75 μM

KYA1797K明显降低了Wnt/β-catenin和MAPK/ERK信号通路的报告基因活性，但并未影响其他与癌症相关途径（如Notch和TGFβ途径）的报告基因活性，因此，KYA1797K选择性地调控Wnt/β-catenin和Ras/ERK途径。KYA1797K增强了内源性axin、GSK3β和β-TrCP的β-catenin结合亲和力。KYA1797K并未增强APC与β-catenin之间的相互作用。它促进了β-catenin破坏复合体的形成。在剂量依赖性的方式下，KYA1797K降解了CRC细胞系（SW480, LoVo, DLD1和HCT15）中的β-catenin和Ras，同时抑制了细胞增殖。KYA1797K主要通过破坏β-catenin结构和附加的Ras降解来抑制CRC细胞的增殖。KYA1797K直接作用于axin，并调节了β-catenin破坏复合体的构形[1]。

通过腹腔注射（i.p.）给予KYA1797K（25 mg/kg）能在携带APC和KRAS突变的D-MT细胞系移植瘤的小鼠中将肿瘤的重量和体积减少70%。KYA1797K治疗显著降低了β-连环蛋白和Ras蛋白的水平，以及Wnt/β-连环蛋白和Ras信号目标。使用KYA1797K处理的小鼠，其体重未发生变化，肝组织也未见异常。KYA1797K显著减少了肿瘤细胞核内β-连环蛋白和膜上的泛Ras的亚细胞定位。因此，KYA1797K具有抗肿瘤效果[1]。

To assay cell proliferation, HCT15 or SW480 cells are plated at a density of 2 × 104 cells/well, and D-WT or D-MT cells were seeded at a density of 1×104 cells/well in a 24-well plate. The cells are then treated with 25 μM KYA1797K or with control (DMSO) for 72 h. In a 96-well plate, cells are seeded at a density of 3 × 103 cells/well. After 24 h, the cells are treated with KY1220, KYA1797K, IWR-1 or XAV939 for 4 d. Next, MTT reagent is added to each well at a concentration of 0.25 mg/ml. After incubation for 2 h at 37°C, insoluble purple formazan is obtained by removing the medium and incubating in 1 ml (24-well) or 200 μl (96-well) of DMSO for 1 h. The absorbance of the formazan product is determined at 590 nm every 24 h. (Only for Reference)