XAV-939

Catalog No.S1180 Batch:S118005

Technical Data

Formula	C₁₄H₁₁F₃N₂OS
Molecular Weight	312.31	CAS No.	284028-89-3
Solubility (25°C)*	In vitro	DMSO	15 mg/mL (48.02 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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.

Targets

TNKS2 ^[1] (Cell-free assay)	TNKS1 ^[1] (Cell-free assay)
4 nM	11 nM

In vitro

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. ^[1]

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. ^[2]

In vivo

AV-939 (NVP-XAV939) selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition.

Protocol (from reference)

Cell Assay:^{^[1]}	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.
Animal Study:^{^[3]}	Animal Models Male Sprague-Dawley rats Dosages 3 mg/kg Administration i.p.

Cell Assay:^{^[1]}

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.

Animal Study:^{^[3]}

Animal Models
Male Sprague-Dawley rats
Dosages
3 mg/kg
Administration
i.p.

References

Customer Product Validation

: Data from [Data independently produced by Nat Commun, 2014, 5, 5455]

: Data from [Data independently produced by Dis Model Mech, 2014, 7(10), 1193-203]

: , , Cancer Lett, 2017, 400:194-202

: , , Dr. Marco Quarta of Stanford University

Selleck's XAV-939 has been cited by 372 publications

Double-Network DNA Macroporous Hydrogel Enables Aptamer-Directed Cell Recruitment to Accelerate Bone Healing [ Adv Sci (Weinh), 2024, 11(1):e2303637]	PubMed: 37949678
BIRC6 Modulates the Protein Stability of Axin to Regulate the Growth, Stemness, and Resistance of Renal Cancer Cells via the β-Catenin Pathway [ ACS Omega, 2024, 9(7):7782-7792]	PubMed: 38405482
Activation of wnt/β-catenin signaling pathway down regulated osteogenic differentiation of bone marrow-derived stem cells in an anhidrotic ectodermal dysplasia patient with EDA/EDAR/EDARADD mutation [ Heliyon, 2024, 10(1):e23057]	PubMed: 38169761
Li-Mg-Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration [ Bioact Mater, 2023, 28:227-242]	PubMed: 37292230
Elevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway [ Nat Commun, 2023, 14(1):3801]	PubMed: 37365192
Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/β-catenin pathway [ Cell Death Dis, 2023, 14(10):696]	PubMed: 37875515
ASCL2 induces an immune excluded microenvironment by activating cancer-associated fibroblasts in microsatellite stable colorectal cancer [ Oncogene, 2023, 42(38):2841-2853]	PubMed: 37591954
Modeling human ectopic pregnancies with trophoblast and vascular organoids [ Cell Rep, 2023, 42(6):112546]	PubMed: 37224015
Dynamic interplay between IL-1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration [ Cell Rep, 2023, 42(6):112647]	PubMed: 37330908
Stromal-induced epithelial-mesenchymal transition induces targetable drug resistance in acute lymphoblastic leukemia [ Cell Rep, 2023, 42(7):112804]	PubMed: 37453060

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