XAV-939
XAV939 (CAS 284028-89-3) is a cell-permeable small molecule inhibitor, functioning as an inhibitor of tankyrase enzymes, particularly targeting TNKS1 and TNKS2, and exhibiting potent inhibitory activity in cellular models involving Wnt/β-catenin signaling regulation. Additionally, it acts as a modulator of osteogenic differentiation in human mesenchymal stem cells (hMSCs).
In experimental studies, XAV939 demonstrates effective inhibition of tankyrase 1 and tankyrase 2 with IC50 values of 5 nM and 2 nM, respectively, tested against purified enzyme assays. It can also enhance osteoblastic differentiation in hMSCs, contributing to increased expression of osteogenic markers and mineralization. Moreover, XAV939 stabilizes axin proteins, thereby promoting degradation of β-catenin and subsequently downregulating Wnt/β-catenin target gene expression at the molecular level.
In disease-related research applications, XAV939 is widely used for investigating diseases associated with aberrant Wnt/β-catenin signaling, such as various cancers, fibrotic diseases, and conditions characterized by diminished bone formation. By selectively inhibiting tankyrase activity and modulating pathway-specific cellular processes, XAV939 serves as an important tool compound for dissecting Wnt pathway-mediated mechanisms and for the preclinical evaluation of novel therapeutics targeting these pathways.
- 1. Houbo Jiang, Zichun Xiao, et al. "Generation of human induced pluripotent stem cell-derived cortical neurons expressing the six tau isoforms." J Alzheimers Dis. 2025 Apr 23:13872877251334831. PMID: 40267294
- 2. Seung Hoan Choi, Sean J. Jurgens, Ling Xiao et al. "Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk." Nat Genet. 2025 Mar;57(3):548-562. PMID: 40050430
- 3. Liu Ruojing, Zhao Xue, et al. "Ginsenoside Rb1 alleviates cerebral ischemic injury in mice by regulating microglial polarization." Chinese Journal of Tissue Engineering Research 2025, Vol. 29 Issue (29): 6219-6227
- 4. Matthew C Hill , Bridget Simonson, et al. "Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation." Nat Commun. 2024 Nov 19;15(1):10002 PMID: 39562555
- 5. Zengfa Deng, Dianbo Long, et al. "IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2." Bone Res. 2024 Oct 28;12(1):63 PMID: 39465252
- 6. Chengjia You, Fangyuan Shen, et al. "O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis." EMBO Rep. 2024 Sep 10. PMID: 39256595
- 7. Anant Chopra, Ruifan Pei, et al. "HSBP7 Rescue of a Titin Cardiomyopathy Identified by Morphological Profiling." Research Square. 08 Jul, 2024
- 8. 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
- 9. 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
- 10. 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
- 11. 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
- 12. 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
- 13. 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
- 14. 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 |
| Synonyms | NVP-XAV939 |
| 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 | O=C1N=C(c2ccc(C(F)(F)F)cc2)NC2=C1CSCC2 |
| 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 flow 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 myofibroblasts and the hydroxyproline content were also significantly 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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