XAV-939

XAV-939
Product Name XAV-939
CAS No.: 284028-89-3
Catalog No.: CFN60028
Molecular Formula: C14H11F3N2OS
Molecular Weight: 312.31 g/mol
Purity: >=98%
Type of Compound: Alkaloids
Physical Desc.: Powder
Targets: Wnt/β-catenin
Source:
Solvent: Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Price:
XAV-939 (NVP-XAV939) selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition with IC50 of 11 nM/4 nM in cell-free assays, regulates axin levels and does not affect CRE, NF-κB or TGF-β.
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Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).

Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.

Need more advice on solubility, usage and handling? Please email to: service@chemfaces.com

The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.
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    Nature,2009 Oct 1;461(7264):614-20.
    Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling.[Pubmed: 19759537]
    The stability of the Wnt pathway transcription factor beta-catenin is tightly regulated by the multi-subunit destruction complex. Deregulated Wnt pathway activity has been implicated in many cancers, making this pathway an attractive target for anticancer therapies. However, the development of targeted Wnt pathway inhibitors has been hampered by the limited number of pathway components that are amenable to small molecule inhibition.
    METHODS AND RESULTS:
    Here, we used a chemical genetic screen to identify a small molecule, XAV939, which selectively inhibits beta-catenin-mediated transcription. XAV939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway.
    CONCLUSIONS:
    Thus, our study provides new mechanistic insights into the regulation of axin protein homeostasis and presents new avenues for targeted Wnt pathway therapies.
    Aging (Albany NY),2010 Oct;2(10):691-708.
    Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs.[Pubmed: 21037379]
    Cell lines:WTK1 lymphoblasts
    Concentrations: 1.0 μM
    Incubation Time:  8 hours
    Method:
    XAV-939 is solubilized in DMSO at 55 °C to make a 10 mM stock solution which may be diluted later to a working concentration of 100 μM. WTK1 lymphoblasts treated with either DMSO or 1.0 μM XAV-939 for 8 hours are loaded into independent wells of a 4-20% gradient SDS-PAGE every 2 hours over the course of 6 hours. At each time point, DMSO and XAV-939 samples are loaded into wells immediately adjacent to the prior time point. The corresponding load times at 0, 2 and 4 hours results in total run times of 2, 4 and 6 hours respectively. The gel is analyzed via western blot for DNA-PKcs following completion of the final run time and is quantified after normalization to actin loading controls.
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