Wnt-C59 --- Wnt Antagonist

Wnt-C59 is a very potent and highly selective Wnt signaling antagonist with an IC50 ~ 74 pM in the Wnt signaling reporter assay. It prevents palmitylation of Wnt proteins by Porcupine (a membrane-bound O-acyltransferase), thereby blocking Wnt protein secretion and activity. Wnt-C59 displayed good bioavailability as once daily oral administration and blocked progression of mammary tumors in MMTV-WNT1 transgenic mice model while downregulating Wnt/β-catenin target genes. Because Wnt-C59 exhibits much better potency and selectivity than the reported IWP series of Porcupine/Wnt inhibitors, it serves as the better Wnt pathway inhibitor for in vitro and in vivo studies.

Product information

CAS Number: 1243243-89-1

Molecular Weight: 379.45

Formula: C25H21N3O

Chemical Name: 2-(4-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide

Smiles: CC1=CC(=CC=N1)C1C=CC(CC(=O)NC2C=CC(=CC=2)C2=CN=CC=C2)=CC=1

InChiKey: KHZOJCQBHJUJFY-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 50 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Wnt-C59 was used at 0.1-0.2 µM to completely block Wnt protein secretion. When used at 0.5 µM, it can be used functionally replace the Dkk protein in many assay conditions.

In Vivo:

Wnt-C59 was used to dose mice orally at 5-10 mg/kg once per day or 5 mg/kg twice per day.

References:

1. Proffitt KD, et al. Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. (2012) Cancer Res. In press.
2. Chen D, et al. (N-(HETERO)ARYL,2-(HETERO)ARYL-SUBSTITUTED ACETAMIDES FOR USE AS WNT SIGNALING MODULATORS. PCT WO/2010/101849.
3. Chen B, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. (2009) Nat Chem Biol. 5(2):100-7.
4. Dodge ME, et al. Diverse chemical scaffolds support direct inhibition of the membrane bound O-acyltransferase Porcupine. (2012) J Biol Chem. 287 (27), pp. 23246–23254
5. Willems E, et al. Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. (2011) Circ Res.109(4):360-4.

Products are for research use only. Not for human use.