Description
GNF-1331 is a Potent, Selective, and Orally Bioavailable Porcupine Inhibitor (IC50 = 12 nM). Blockade of aberrant Wnt signaling is an attractive therapeutic approach in multiple 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, such as cutaneous squamous cell carcinoma (SCC), breast cancer, and colorectal cancer.
Uses
GNF-1331 (compound 19) is a potent, selective and orally bioavailable porcupine inhibitor (IC50=12 nM). GNF-1331 blocks Wnt ligand secretion and subsequent Wnt signaling activity, and induces significant antitumor effects in the mouse MMTV-WNT1 xenograft tumor model[1].
in vivo
GNF-1331 shows good potency in the Wnt secretion coculture assay with an IC50 of 12 nM. It binds to PORCN in a radioligand binding assay with an IC50 of 8 nM. However, it exhibits poor pharmacokinetic properties with rapid clearance and low systemic exposure after oral administration in mice (dose normalized Cmax and AUC are 0.03 μM·h and 0.014 μM, respectively), which prevent it from being used in vivo._x000D_
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Reference: ACS Med Chem Lett. 2016 May 10;7(7):676-80. https://pubmed.ncbi.nlm.nih.gov/27437076/
target
GNF-1331 is a Potent, Selective, and Orally Bioavailable Porcupine Inhibitor (IC50 = 12 nM).
References
[1] Dai Cheng, et al. "Discovery of pyridinyl acetamide derivatives as potent, selective, and orally bioavailable porcupine inhibitors." ACS medicinal chemistry letters 7.7 (2016): 676-680. DOI:
10.1021/acsmedchemlett.6b00038
