ETC-159 is a potent, orally available PORCN inhibitor. It inhibits β-catenin reporter activity with an IC50 of 2.9 nM.
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[1]
ETC-159 inhibits mouse PORCN with an IC50 of 18.1 nM, whereas the IC50 for Xenopus Porcn is approximately four fold higher (70 nM). 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 5 mg/kg, ETC-159 is rapidly absorbed into the blood with a Tmax of ~0.5 h and oral bioavailability of 100%[1].
References:
[1]. Madan B, et al. Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene. 2015 Aug 10. doi: 10.1038/onc.2015.280.