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ETC-159 is a potent and orally bioavailable inhibitor of porcupine (PORCN; IC50s = 18.1 and 70 nM for mouse and Xenopus PORCN, respectively).1 It inhibits β-catenin reporter activity (IC50 = 2.9 nM) and reduces the interaction of Wnt with its carrier protein WLS via decreased Wnt palmitoleation in STF3A cells, an effect that is reversed by overexpression of recombinant PORCN. ETC-159 inhibits PA-1 teratocarcinoma colony formation in soft agar (IC50 = 35 nM). In vivo, ETC-159 (1-10 mg/kg) reduces tumor growth in a dose-dependent manner in mice carrying a mouse mammary tumor virus LTR-Wnt1 transgene and in A-1 and NCCIT teratocarcinoma mouse xenograft models. It also reduces growth and induces differentiation in colon adenocarcinoma mouse xenograft models that contain R-spondin (RSPO) translocations.
WARNING This product is not for human or veterinary use.
1. Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene 35(17), 2197-2207 (2016).