GNF-6231

Description: GNF-6231 is a novel, potent, orally active and selective Porcupine inhibitor that blocks Wnt signaling with IC50 of 0.8 nM (Wnt3a Co-culture RGA). GNF-6231 has low/no drug drug interaction potential with IC50s of greater than 10 uM on all CYP isoforms tested. GNF-6231 showed excellent pathway inhibition and induced robust antitumor efficacy in a mouse MMTV-WNT1 xenograft tumor model. Targeting the aberrant Wnt signaling pathway is an attractive approach for the treatment of various cancers. Wnt signaling is tightly controlled during cellular proliferation, differentiation, and embryonic morphogenesis. Aberrant activation of this pathway plays a critical role in a variety of cancers including cutaneous squamous cell carcinoma (SCC), breast cancer, and colorectal cancer.

References: ACS Med Chem Lett. 2016 May 10; 7(7):676-80.