Wnt-C59

Porcupine (PORCN) is a membrane bound O-acyltransferase that mediates palmitoylation of Wnt family proteins. This step is required for secretion and biologic activity of Wnt proteins, which have roles in embryonic development and cancer. Wnt-C59 is a potent inhibitor of PORCN, as measured by prevention of Wnt3A activation (IC50 = 74 pM). As palmitoylation of Wnt is required for its secretion, Wnt-C59 completely blocks Wnt3A secretion into culture media. Wnt-C59 prevents activation of all evaluated Wnt family members. This compound is effective in vivo as well as in vitro. Whether given by intravenous (2.5 mg/kg) or oral administration (5 mg/kg), Wnt-C59 displays a half-life in blood of approximately 1.94 hours, and remains greater than 10-fold above the in vitro IC50 concentration for at least 16 hours after a single oral dose. It blocks the progression of both basal-like and triple-negative breast cancers while downregulating Wnt/beta-catenin pathway target genes in mice.Formal Name: 4-(2-methyl-4-pyridinyl)-N-[4-(3-pyridinyl)phenyl]-benzeneacetamide. CAS Number: 1243243-89-1. Synonyms: PORCN Inhibitor II. Molecular Formula: C25H21N3O. Formula Weight: 379.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml. lambdamax: 275 nm. SMILES: CC1=CC(C2=CC=C(CC(NC3=CC=C(C4=CN=CC=C4)C=C3)=O)C=C2)=CC=N1. InChi Code: InChI=1S/C25H21N3O/c1-18-15-22(12-14-27-18)20-6-4-19(5-7-20)16-25(29)28-24-10-8-21(9-11-24)23-3-2-13-26-17-23/h2-15,17H,16H2,1H3,(H,28,29). InChi Key: KHZOJCQBHJUJFY-UHFFFAOYSA-N.