Stemolecule™ XAV939

Stemolecule XAV939 is a cell-permeable small molecule inhibitor of the Wnt / β-catenin pathway. XAV939 inhibits tankyrase 1 and tankyrase 2, thus stabilizing axin and stimulating β-catenin degradation¹. Current research suggests that Wnt proteins act to maintain stem cells in an undifferentiated, self-renewing state². Wnt proteins act on a variety of stem cells that include neural, mammary and embryonic stem cells. In addition, XAV939 inhibits growth of DLD-1 cells, an APC-deficient colorectal cancer cell line¹.

Specifications

Product Name: Stemolecule XAV939

Catalog Number: 04-0046

Size: 2 mg

Alternate Name(s): 2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-ol

Chemical Formula: C₁₄H₁₁F₃N₂OS

Molecular Weight: 312.31

CAS Number: 284028-89-3

Purity: Greater than 95 % by HPLC analysis

Formulation: White powder

Solubility: XAV939 is reported to be soluble in DMSO at 100 mM.

Reconstitution: For a 10 mM concentrated stock solution of XAV939, reconstitute the compound by adding 640.4 µL of DMSO to the entire contents of the vial. If precipitate is observed, warm the solution to 37 °C for 2 to 5 minutes. For use in cell culture, warm the media prior to adding reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%. 

Storage and Stability: Store powder at −20 °C protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20 °C, protected from light. The effect of storage of stock solutions should be verified for each application.

Quality Control: The purity of XAV939 is determined by HPLC analysis. The molecular weight is determined by mass spectrometry. No acute cytotoxicity is observed in mouse embryonic stem cells following a 6 hour exposure to 1 nM — 100 uM of XAV939.

Documents

Specification Sheets:

• 04-0046 Specifications Sheet

Safety Data Sheets:

• 04-0046 Safety Data Sheet

References

1. Huang, S.M., Mishina, Y.M., Liu, S., Cheung, A., Stegmeier, F., Michaud, G.A., Charlat, O., Wiellette, E., Zhang, Y., Wiessner, S., Hild, M., Shi, X., Wilson, C.J., Mickanin, C., Myer, V., Fazal, A., Tomlinson, R., Serluca, F., Shao, W., Cheng, H., Schultz, M., Rau, C., Schirle, M., Schlegl, J., Ghidelli, S., Fawell, S., Lu, C., Curtis, D., Kirschner, M.W., Lengauer, C., Finan, P.M., Tallarico, J.A., Bouwmeester, T., Porter, J.A., Bauer, A., and Cong, F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signaling. Nature 461: 614-620 (2009)
2. Nusse, R. Wnt signaling and stem cell control. Cell Research 18: 523-527 (2008).

Additional Publications

• Zhang A; Sokolva I; Domissy A; Davis J; rao L; Utami KH; Wang Y; Hagerman RJ; Pouladi MA; Sanna P; Bolad MH; Loring JF. Maturation Delay of Human GABAergic Neurogenesis in Fragile X Syndrome Pluripotent Stem Cells. Stem Cells Transl Med 11:613 (2022).
• Wang M; Li W; Hao J; Conzales A; Zhao Z; Flores RS; Kuang X; Mu X; Ching T; Tang G; Luo Z; Garciamendez-Mijares EC; Sahoo JK; Wells MF; Niu G; Agrawal P; Quiñonoes-Hinojosa A; Eggan K; Zhang YS. Molecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues. Nature Commun 13:3317 (2022).
• Li J; Chen : Li D; Lu M; Huang X; Han X; Chen H. Electroacupuncture Promotes the Survival of the Grafted Human MGE Neural Progenitors in Rats with Cerebral Ischemia by Promoting Angiogenesis and Inhibiting Inflammation. Neural Plasticity 2021:4894881 (2021).
• Ressler AK. Reading the Disease Leaves: Signals, signatures and synchrony in neurodevelopmental disorders. Ph. D. Thesis, Columbia University : (2021).
• Susco SG; Arias-Garçia MA; López-Huerta VG; Beccard A; Bara AM; Moffitt J; Korn J; Fu Z; Barrett LE. FMR1 loss in a human stem cell model reveals early changes to intrinsic membrane excitability. Develop Biol 468:93-100 (2020).
• Chu J; Fitzgerald ML; Sehgal M; Manley W; Fitzgerald S; Naung H; Goldberg EM; Anderson SA. Enhanced maturation of human stem cell derived interneurons by mTOR activation . bioRxiv :dx.doi.org/10.1101/777714 (2019).
• Graß T. Modeling familial Alzheimer's disease utilizing gene targeted human induced pluripotent stem cells. Doctoral Thesis, Freie Univerität Berlin : (2018).
• Ooi J; Langley SR; Xu X; Utami KH; Sim B; Huang Y; Harmston NP; Tay YL; Ziaei A; Zeng R; Low D; Aminkeng F; Sobota RM; Ginhoux F; Petretto E; Pouladi MA. Unbiased Profiling of Isogenic Huntington Disease hPSC-Derived CNS and Peripheral Cells Reveals Strong Cell-Type Specificity of CAG Length Effectsty of CAG Length Effects. Cell Reports 26:2494-508.e7 (2019).
• Duong TT; Lim J; Vasireddy V; Papp T; Nguyen H; Leo L; Pan J; Zhou S; Chen HI; Bennet J; Mills JA. Comparative AAV-eGFP Transgene Expression Using Vector Serotypes 1–9, 7m8, and 8b in Human Pluripotent Stem Cells, RPEs, and Human and Rat Cortical Neurons. Stem Cells Int:Article ID: 7281912 (2019).
• Ye P; Chiang YJ; Qi Z; Li Y; Wang S; Liu Y; Li X; Chen Y-G. Tankyrases maintain homeostasis of intestinal epithelium by preventing cell death. PLoS Genetic 14(9):E1007697 (2018).
• Tu J; Cap D; Li L; Cheung H-H; Chan W-Y. MicroRNA profiling during directed differentiation of cortical interneurons from human-induced pluripotent stem cells. FEBS Open Bio 8:502-512 (2018).
• Magadum A; Ding Y; He L; Kim T; Vasudevarao MD; Long Q; Yang K Wickramasinghe N; Renikunta HV; Dubois N; Veidinger G; Yang Q; Engel FB. Live cell screening platform identifies PPARγ as a regulator of cardiomyocyte proliferation and cardiac repair. Cell Res 27:1002 (2017).
• Xu X; Radulescu CI; Utami KH; and Pouladi MA. Obtaining Multi-electrode Array Recordings from Human Induced Pluripotent Stem Cell−Derived Neurons. Bio-protocol 7:e2609 (2017).
• Itokazu T; Hayano Y; Takahashi R; Yamashita T. Involvement of Wnt/β-catenin signaling in the development of neuropathic pain. Neurosci Res 79:34 (2014).
• Voutilainen M; Lindfors PH; Trela EW; Lonnblad D; Shirokova V; Ela T; Rysit R; Schmidt-Ulrich R; Schneider P; Mikkola ML. Ectodysplasin/NF-κB promotes mammary cell fate via Wnt/β-catenin pathway. PLoS Genet 11(11): e1005676. doi:10.1371/journal.pgen.1005676 (2015).