ETC-159 is a potent and specific inhibitor of Wnt secretion. ETC-159 inhibits β-catenin reporter activity in a dose-dependent manner with an IC50 of 2.9nM.
信号通路
Stem Cells & Wnt
靶点
Wnt
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IC50
2.9nM
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体外研究
ETC-159 blocks the secretion and activity of all Wnts. ETC-159 has robust activity in multiple cancer models driven by high Wnt signaling. ETC-159 is highly efficacious in molecularly defined colorectal cancers (CRCs) with R-spondin translocations.
体内研究
ETC-159 inhibits mouse PORCN with an IC50 of 18.1nM, whereas the IC50for Xenopus Porcn was approximately fourfold higher (70nM). ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. ETC-159 exhibits good oral pharmacokinetics in mice allowing preclinical evaluation via oral administration. After a single oral dose of 5mg/kg, ETC-159 is rapidly absorbed into the blood with a Tmax of ~0.5h and oral bioavailability of 100%.