XAV-939
XAV-939 is a small-molecule inhibitor of tankyrase 1/2 with IC50 values of 4 and 11 nM, respectively [1].
XAV-939 was screened out as an inhibitor of Wnt/β-catenin pathway. In HEK293 cells, XAV-939 significantly inhibited the Wnt3a-stimulated STF activity and β-catenin accumulation. In SW480 cells, XAV-939 also inhibited STF activity and increased β-catenin phosphorylation. XAV-939 was demonstrated to stabilize the axin levels through inhibiting tankyrases and subsequently inhibit the Wnt signaling. It tightly bound to the catalytic domains of tankyrase 1 and tankyrase 2 with Kd values of 99 and 93 nM, respectively. In addition, XAV-939 significantly inhibited colony formation of β-catenin-dependent DLD-1 cells but not β-catenin-independent RKO cells [1].
References:
[1] Huang S M A, Mishina Y M, Liu S, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature, 2009, 461 (7264): 614-620.
- 1. Zhi-Hong Yang, Ye-Ju Liu, et al. "Pterostilbene alleviated cerebral ischemia/reperfusion-induced blood–brain barrier dysfunction via inhibiting early endothelial cytoskeleton reorganization?and late basement membrane degradation." Food Funct. 2023 Aug 21. PMID: 37602757
- 2. Marisol Romero-Tejeda, Hananeh Fonoudi, et al. "A novel transcription factor combination for direct reprogramming to a spontaneously contracting human cardiomyocyte-like state." J Mol Cell Cardiol. 2023 Sep:182:30-43. PMID: 37421991
- 3. Luo Y, Ge S, et al. "Overexpression of FoxM1 optimizes the therapeutic effect of bone marrow mesenchymal stem cells on acute respiratory distress syndrome." Stem Cell Res Ther 2023 Feb 14;14(1) PMID: 36788588
- 4. Qiyun Shi, Lu Huang, et al."The effects of jiawei Duhuo Jisheng mixture on Wnt/β-catenin signaling pathway in the synovium inflamed by knee osteoarthritis: An in vitro and in vivo experiment." J Ethnopharmacol. 2022 Aug 10;294:115363. PMID: 35551975
- 5. Shan Lin, Qingui Chen, et al."Overexpression of HOXB4 Promotes Protection of Bone Marrow Mesenchymal Stem Cells Against Lipopolysaccharide-Induced Acute Lung Injury Partially Through the Activation of Wnt/β-Catenin Signaling." J Inflamm Res. 2021 Jul 27;14:3637-3649. PMID: 34349541
- 6. Grunewald ME, Chen Y, et al. "The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression." PLoS Pathog. 2019 May 16;15(5):e1007756. PMID: 31095648
- 7. Jia J, Qiao Y, et al."Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade." PLoS One. 2017 Sep 6;12(9):e0184068. PMID: 28877210
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 312.31 |
| Cas No. | 284028-89-3 |
| Formula | C14H11F3N2OS |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥15.62 mg/mL in DMSO |
| Chemical Name | 2-[4-(trifluoromethyl)phenyl]-1,5,7,8-tetrahydrothiopyrano[4,3-d]pyrimidin-4-one |
| SDF | Download SDF |
| Canonical SMILES | C1CSCC2=C1NC(=NC2=O)C3=CC=C(C=C3)C(F)(F)F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
HCT116 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
20 μM, 24 hours |
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Applications |
HCT116 cells were treated with XAV-939, then stained with PI and subjected to ?ow cytometric analysis or lysed and subjected to immunoblot analysis. The results showed that the number of cells arrest in G1 phase was 71.01%, as compared with the 45.54% of untreated control samples. Western blot analysis revealed that XAV-939 increased the level of AXIN and inhibited the expression of β-catenin. |
| Animal experiment: [2] | |
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Animal models |
Mice |
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Dosage form |
Intraperitoneal injection, 2.5 mg/kg, four times a day |
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Applications |
Treatment of bleomycin challenged mice with XAV-939 reduced dermal thickening by 50% compared with sham-treated, bleomycin challenged mice. The number of myo?broblasts and the hydroxyproline content were also signi?cantly decreased in mice treated with XAV-939. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] He L, Lu N, Dai Q, et al. Wogonin induced G1 cell cycle arrest by regulating Wnt/β-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells. Toxicology, 2013, 312: 36-47. [2] Distler A, Deloch L, Huang J, et al. Inactivation of tankyrases reduces experimental fibrosis by inhibiting canonical Wnt signalling. Annals of the rheumatic diseases, 2013, 72 (9): 1575-1580. |
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| XAV-939 is a inhibitor of TNKS1 and TNKS2 with IC50 of 11 and 4 nM, respectively. | ||||||
| Targets | TNKS1 | TNKS2 | ||||
| IC50 | 11 nM | 4 nM | ||||
Quality Control & MSDS
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