product name XAV-939
Description: XAV-939 (also known as NVP-XAV939) selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition with IC50 of 11 nM/4 nM in cell-free assays, it regulates axin levels and does not affect CRE, NF-κB or TGF-β. XAV-939 antagonizes Wnt signaling via stimulation of β-catenin degradation and stabilization of axin. XAV-939 inhibits proliferation of the μ-catenin-dependent colon carcinoma cell line DLD-1. and promotes cardiomyogenic development in mesoderm progenitor cells.
References: Aging (Albany NY). 2010 Oct;2(10):691-708; Nature. 2009 Oct 1;461(7264):614-20.
312.31
Formula
C14H11F3N2OS
CAS No.
284028-89-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 12 mg/mL (38.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% PEG 400+0.5% Tween 80+5% Propylene glycol: 30mg/mL
Synonyms
NVP-XAV939
other peoduct :
| In Vitro |
In vitro activity: XAV-939 specifically inhibits tankyrase PARP activity. XAV-939 dramatically decreases DNA-PKcs protein levels, confirming the critical role of tankyrase poly-ADP-ribosylation activity in maintaining stability of the DNA-PKcs protein. The greatest reduction of DNA-PKcs protein levels (< 25% relative expression compared to DMSO treated controls) occurs at 12 hours with 1.0 μM XAV-939 exposure. Treatment of human lymphoblasts with 1.0 μM XAV-939 results in marked elevation of tankyrase 1 levels. XAV-939 is axin stabilizing agent. XAV-939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. XAV-939 stabilizes axin by blocking 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. XAV-939 deregulates the Wnt/b-catenin pathway which has been implicated in many cancers. Kinase Assay: Cell Assay: 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. |
|---|---|
| In Vivo | Treatment of bleomycin challenged mice with XAV-939 reduced dermal thickening by 50% compared with sham-treated, bleomycin challenged mice. The number of myofibroblasts and the hydroxyproline content were also significantly decreased in mice treated with XAV-939. |
| Animal model | Mouse model |
| Formulation & Dosage | 2.5 mg/kg; i.p. injection |
| References | Nature. 2009 Oct 1;461(7264):614-20; Ann Rheum Dis. 2013 Sep 1;72(9):1575-80. |
