ETC-159 (C09-0880-798)

InformationETC-159 ETC-159 (ETC-1922159) is an orally available, potent porcupine inhibitor with an IC50 of 2.9 nM for inhibiting β-catenin reporter activity in STF3A cells.TargetsPorcnIn vitroETC-159 treatment causes decreased abundance of Wnt3a-stabilized β-catenin protein in both mouse L cells and HEK293 cells. ETC-159 inhibits β-catenin signaling in response to multiple active Wnts. ETC-159 inhibits mouse PORCN with an IC50 of 18.1/u2009nM, whereas the IC50 for Xenopus Porcn is approximately fourfold higher (70/u2009nM).In vivoETC-159 is orally bioavailable and effectively inhibits the growth of mouse mammary tumor virus-Wnt1 tumors. After a single oral dose of 5/u2009mg/kg in mice, ETC-159 is rapidly absorbed into the blood with a Tmax of ~0.5/u2009h and oral bioavailability of 100%. The plasma half-life is ~1.18/u2009h and its concentration in the blood remained above the in vitro IC50 for at least 16/u2009h. Treatment of mice with increasing doses of ETC-159 leads to a dose-related increase in exposure. ETC-159 also effectively inhibits Wnt autocrine signaling and growth of teratocarcinomas. ETC-159 effectively inhibits the growth and induces differentiation of colon cancers with RSPO translocations and induces global remodeling of gene expression. Suppression of Wnt/β-catenin signaling with ETC-159 in genetically defined tumors induces irreversible cellular differentiation thus preventing regrowth of these tumors.Cell Research(from reference)Cell lines：Mouse L cells Concentrations：100/u2009nM Incubation Time：0-24 h. Specification: 0.98 Molecular Formula: C19H17N7O3 Molecular Weight: 391.38 PubChem CID: 86280523 Isomeric SMILES: CN1C2=C(C(=O)N(C1=O)C)N(C=N2)CC(=O)NC3=NN=C(C=C3)C4=CC=CC=C4