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Purity: ≥98%
XAV-939 (also called NVP-XAV 939; XAV939; NVP XAV939; XAV-939) is a potent inhibitor of the TNKS (Tankyrase) with IC50 values of 0.011 and 0.004 μM for inhibiting TNKS1 and TNKS2 respectively. It selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition and 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.
| Targets |
TNKS2: 2 nM (IC50)
TNKS1: 5 nM (IC50) ARTD2: 479 nM (IC50) ARTD1: 5500 nM (IC50) |
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| ln Vitro |
IC50 values for XAV-939 against TNKS1 and TNKS2 are 5 nM and 2 nM, respectively[1]. For three or ten days, XAV-939 (0.3–30 μM) improves the osteoblastic development of hBMSCs [2]. By causing SH3BP2 to accumulate, XAV-939 (3 μM) stimulates the osteoblastic differentiation of hMSCs [2]. During osteoblast development, XAV-939 (3 μM; 10 days) increases the expression of OPG and decreases the expression of RANKL in hBMSC cells [2]. XAV-939 stimulates the production of SFRP3 and SFRP4, while suppressing Wnt/β-catenin signaling [3].
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| ln Vivo |
In vivo, XAV-939 restores cartilage degeneration brought on by mechanical stress [3].
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| Enzyme Assay |
Screening of Inhibitors and Measurement of Inhibitor Potencies [1]
Flavone derivatives with only one substitution were identified by searching commercially available compound libraries and purchased from different vendors through Molport. The compounds were stored at −20 °C in DMSO and were diluted in the TNKS1 assay buffer before adding them into the reaction mixtures. The compounds were tested at 10 and 1 μM in duplicate. Compound controls were used in this screening to exclude the effect of compound fluorescence and quenching. Inhibition potencies were measured for the inhibitors that had IC50 values below 10 μM based on the two-point initial screening. IC50 values were measured using half log dilutions, and reactions were carried out three individual times in quadruplicate for TNKS1. The incubation time was adjusted so that substrate conversion was more than 50% in the case of screening and less than 30% in the case of IC50 measurement. Dose–response curves were fitted using four parameters with Graphpad Prism (version 5.0 for Windows). [1] Profiling of the Inhibitors [1] The best tankyrase inhibitors identified were also profiled against six other human ARTD family members using the homogeneous activity assay described above. Incubation times and conditions varied for each enzyme based on optimization carried out previously. The substrate NAD+ concentration was 250 or 500 nM in the profiling assays. In order to obtain a robust signal, the incubation time was adjusted so that substrate conversion was more than 50% in each case. In order to efficiently evaluate the selectivity of the compounds, they were profiled at 1 μM. DMSO, compound, and protein controls were used with all the enzymes to exclude or correct for the effects of DMSO, autofluorescence, and quenching of the fluorescence. |
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: hMSC-TERT cell line Tested Concentrations: 0.3, 3, and 30 μM Incubation Duration: 3 days Experimental Results: demonstrated no significant effect on proliferation at day 1, 2, and 3 at dose of 0.3 and 3 μM but inhibited hMSCs cell proliferation on day 3 at dose of 30 μM. Apoptosis Analysis[2] Cell Types: hMSC-TERT cell line Tested Concentrations: 3 μM Incubation Duration: 3 days Experimental Results: demonstrated a minute percentage of cell death (apoptosis and necrosis ) in the XAV-939-treated hBMSC RT-PCR[2] Cell Types: hMSC-TERT cell line Tested Concentrations: 3 µM Incubation Duration: 10 days Experimental Results: Upregulated gene expression of osteoblast-associated gene markers including: ALP, COL1A1, RUNX2, and OC. |
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| Animal Protocol |
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| References |
[1]. Mohit Narwal, et al. Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity. J Med Chem. 2013 Oct 24;56(20):7880-9.
[2]. Nuha Almasoud, et al. Tankyrase inhibitor XAV-939 enhances osteoblastogenesis and mineralization of human skeletal (mesenchymal) stem cells. Sci Rep. 2020 Oct 7;10(1):16746. [3]. Senxin Cai, et al. Mechanical stress reduces secreted frizzled-related protein expression and promotes temporomandibular joint osteoarthritis via Wnt/β-catenin signaling. Bone. 2022 Aug;161:116445. |
| Molecular Formula |
C14H11F3N2OS
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| Molecular Weight |
312.31
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| Exact Mass |
312.05441
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| Elemental Analysis |
C, 53.84; H, 3.55; F, 18.25; N, 8.97; O, 5.12; S, 10.27
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| CAS # |
284028-89-3
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| tPSA |
66.8Ų
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| SMILES |
S1C([H])([H])C2C(N([H])C(C3C([H])=C([H])C(C(F)(F)F)=C([H])C=3[H])=NC=2C([H])([H])C1([H])[H])=O
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| InChi Key |
KLGQSVMIPOVQAX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H11F3N2OS/c15-14(16,17)9-3-1-8(2-4-9)12-18-11-5-6-21-7-10(11)13(20)19-12/h1-4H,5-7H2,(H,18,19,20)
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| Chemical Name |
2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[4,3-d]pyrimidin-4(5H)-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ～1.6 mg/mL (5.0 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can take 100 μL of 16 mg/mL DMSO stock solution and add to 400 μL of PEG300, mix well; Then add 50 μL of Tween 80 to the above solution, mix well; Finally, add 450 μL of saline to the above solution, mix well. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Solubility in Formulation 2: ～1.6 mg/mL (5.0 mM) in 10% DMSO + 90% (20% SBE-β-CD in saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can take 100 μL of 16 mg/mL DMSO stock solution and add to 900 μL of 20% SBE-β-CD in saline, mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ～1.6 mg/mL (5.0 mM) in 10% DMSO + 90% Corn oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can take 100 μL of 16 mg/mL DMSO stock solution and add to 900 μL of corn oil, mix well. Solubility in Formulation 4: ～5 mg/mL (16.0 mM) in 50% PEG300 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution. Solubility in Formulation 5: ～30 mg/mL (96 mM) in 30% PEG 400+0.5% Tween 80+5% Propylene glycol (add these co-solvents sequentially from left to right, and one by one). (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2019 mL | 16.0097 mL | 32.0195 mL | |
| 5 mM | 0.6404 mL | 3.2019 mL | 6.4039 mL | |
| 10 mM | 0.3202 mL | 1.6010 mL | 3.2019 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.
Calculation results
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.
(2) Be sure to add the solvent(s) in order.
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