Wnt-C59

Alias: WntC59; C-59; Wnt-C 59; C59; Wnt-C59; C 59;2-(4-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide
Cat No.:V1352 Purity: ≥98%
Wnt-C59 (also called Wnt-C 59;C59;Wnt-C-59; C-59) is a novel, highly potent and orally bioactive PORCN (porcupine) inhibitor with potential antineoplastic activity.
Wnt-C59 Chemical Structure CAS No.: 1243243-89-1
Product category: Wntbeta-catenin
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Wnt-C59 (also called Wnt-C 59; C59; Wnt-C-59; C-59) is a novel, highly potent and orally bioactive PORCN (porcupine) inhibitor with potential antineoplastic activity. It inhibits Wnt3A-mediated activation of a multimerized TCF-binding site driving luciferase with an IC50 of 74 pM in HEK293 cells. Wnt-C59 has a different selectivity with the reported Wnt inhibitor crizotinib. When tested with HT1080 and Hela cells, Wnt-C59 showed inhibition on activation of a multimerized TCF-binding site driving luciferase mediated by Wnt3A by completely abrogating Wnt secretion. Wnt-C59 displays good bioavailability in mice. Wnt-C59 blocks progression of mammary tumors in MMTV-WNT1 transgenic mice while downregulating Wnt/β-catenin target genes. Wnt-C59 has the potential to eradicate cancer stem cells in human tumors. Wnt-C59 inhibits stemness properties of NPC cells in a dosage-dependent manner by arresting sphere formation in both HNE1 and SUNE1 cells.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
As determined by blocking Wnt palmitoylation, Wnt interaction with the carrier protein Wntless/WLS, Wnt secretion, and Wnt activation of β-catenin reporter activity, Wnt-C59 (C59) reduces PORCN function in vitro at nanomolar concentrations. With an IC50 of 74 pM, Wnt-C59 blocks WNT3A-mediated activation of a multimerized TCF-binding site that drives luciferase[1].
ln Vivo
In mice, wnt-C59 exhibits good bioavailability. Wnt-C59 downregulates Wnt/β-catenin target genes while preventing the growth of breast cancers in MMTV-WNT1 transgenic mice[1]. In human cancers, Wnt-C59 has the ability to eliminate cancer stem cells. Wnt-C59 stops the creation of spheres in both HNE1 and SUNE1 cells, which suppresses the stemness characteristics of NPC cells in a dosage-dependent manner[2].
Animal Protocol
Dissolved in 0.5% methylcellulose and 0.1% Tween-80; 10 mg/kg; Oral gavage
Female nude mice orthotopically transplanted with independent MMTV-WNT1 tumors
References
[1]. Proffitt KD, et al. Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res. 2013 Jan 15;73(2):502-7.
[2]. Cheng Y, et al. Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in mice by inhibiting the Wnt pathway in the tumor microenvironment. Oncotarget. 2015 Jun 10;6(16):14428-39.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C25H21N3O
Molecular Weight
379.45
CAS #
1243243-89-1
SMILES
O=C(NC1=CC=C(C2=CC=CN=C2)C=C1)CC3=CC=C(C4=CC(C)=NC=C4)C=C3
Synonyms
WntC59; C-59; Wnt-C 59; C59; Wnt-C59; C 59;2-(4-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 76 mg/mL (200.3 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
Solubility (In Vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O:5 mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.6354 mL 13.1770 mL 26.3539 mL
5 mM 0.5271 mL 2.6354 mL 5.2708 mL
10 mM 0.2635 mL 1.3177 mL 2.6354 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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