XAV-939
(Synonyms: 3,5,7,8-四氢-2-[4-(三氟甲基)苯基]-4H-噻喃并[4,3-D]嘧啶-4-酮) 目录号 : GC12781
XAV-939 选择性抑制 β-连环蛋白介导的转录。
Cas No.:284028-89-3
Sample solution is provided at 25 µL, 10mM.
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XAV-939 selectively inhibits β-catenin-mediated transcription. XAV-939 stimulates β-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2 with IC50 values of 5 nM and 2 nM, respectively [1，2].
XAV-939 inhibited mouse neurofibroma sphere formation with IC50 of 0.1 μM. Western blot confirmed a 50% decrease in total β-catenin with 3 days of XAV-939 exposure (10 nM) [3]. TNKS1 plays a role in cell cycle regulation and that XAV-939 induces an accumulation of NB cell lines at G2/M and S phase of the cell cycle [4].
XAV-939 increases Irradiation (IR) sensitivity of cervical cancer with the PIK3CA-E545K mutation in vivo, XAV-939 and IR inhibited tumor weight by 38% from IR alone in that with PIK3CA-WT [5]. Combinatorial inhibition of transforming growth factor-β (TGF-β) and WNT signaling with SB431542 and XAV-939 potently enhances the efficiency, quality, and speed of reprogrammed iCMs generated upon delivery of the minimal transcription factor (TF) cocktail, GMT, into postnatal cardiac fibroblasts. SB431542 and XAV-939 significantly improved in vivo reprogramming and cardiac function in mice compared with GMT alone and reduced the number of TFs needed for human reprogramming [6].
References:
[1]. S.M. Huang, Y.M. Mishina, S. Liu, A. Cheung, F. Stegmeier, G.A. Michaud, O. Charlat, E. Wiellette, Y. Zhang, S. Wiessner, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signaling.Nature, 461 (2009), pp. 614-620
[2]. 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.
[3]. Wu J, Keng VW, Patmore DM, et al. Insertional mutagenesis identifies a STAT3/Arid1b/beta-catenin pathway driving neurofibroma initiation. Cell Rep. 2016;14:1979-90.
[4]. X.H. Tian, W.J. Hou, Y. Fang, J. Fan, H. Tong, S.L. Bai, et al. XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway. J Exp Clin Cancer Res, 32 (1) (2013 Dec 5), p. 1
[5]. Jiang W, Wu Y, He T, et al. Targeting of beta-catenin reverses radioresistance of cervical cancer with the PIK3CA E545K mutation. Mol Cancer Ther 2020;19(2):337-47.
[6]. Mohamed, T. M. et al. Chemical enhancement of in vitro and in vivo direct cardiac reprogramming. Circulation 135, 978-995 (2017).
XAV-939 选择性抑制 β-连环蛋白介导的转录。 XAV-939 通过稳定轴蛋白（破坏复合物的浓度限制成分）来刺激 β-连环蛋白降解。 XAV939 通过抑制多聚 ADP 核糖基化酶 tankyrase 1 和 tankyrase 2 来稳定 axin，IC50 值分别为 5 nM 和 2 nM [1，2]。
XAV-939 抑制小鼠神经纤维瘤球体形成，IC50 为 0.1 μM。 Western blot 证实，XAV-939 暴露 (10 nM) 3 天后，总 β-连环蛋白减少了 50% [3]。 TNKS1在细胞周期调控中发挥作用，XAV-939诱导NB细胞系在细胞周期的G2/M期和S期积累[4]。
XAV-939 在体内增加了具有 PIK3CA-E545K 突变的宫颈癌的辐照 (IR) 敏感性，XAV-939 和 IR 抑制了 38% 的肿瘤重量，与 PIK3CA-WT 单独使用 IR 相比 [5] 。使用 SB431542 和 XAV-939 联合抑制转化生长因子-β (TGF-β) 和 WNT 信号转导，可有效提高将最小转录因子 (TF) 混合物 GMT 递送至细胞内后生成的重编程 iCM 的效率、质量和速度产后心脏成纤维细胞。与单独使用 GMT 相比，SB431542 和 XAV-939 显着改善了小鼠的体内重编程和心脏功能，并减少了人类重编程所需的 TF 数量[6]。
| Cell experiment [1]: | |
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Cell lines |
A549 cells |
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Preparation Method |
A549 cells in the logarithmic growth phase were seeded in 96-well plates, at a density of 2×104 cells/well, and subsequently treated with various XAV-939 concentrations (0.1, 0.5, 1, 5, 10 µmol/l) for 24, 48, 72 and 96 h. |
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Reaction Conditions |
0.1, 0.5, 1, 5, 10 µmol/l for 24, 48, 72 and 96 h |
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Applications |
At all experimental time points, XAV-939 treatment was able to significantly inhibit A549 cell proliferation compared with the control group (F24h=30.382, F48h=52.463, F72h=56.635, F96h=59.274), with the exception of the 5-and 10-µmol/l groups at the 24 h time point. |
| Animal experiment [2]: | |
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Animal models |
DBA/2 inbred mice |
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Preparation Method |
Mice received an intraperitoneal injection of 100 µl of XAV-939 (2 mg/ml) along with a 10% dimethyl sulfoxide (DMSO; compounded by 0.9% NaCl solution) every day since they received vaccination with the L1210 cells, while according to other experimental groups, mice received intraperitoneal injections along with 100 µl of 10% DMSO solution (compounded by 0.9% NaCl solution) for 21 days continuously. |
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Dosage form |
Intraperitoneal injection, 100 µl of 2 mg/ml for 21 days |
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Applications |
In the model, NC, HOTAIR mimics, siRNA HOTAIR, XAV-939, and HOTAIR mimics + XAV-939 groups, the WBC number in PB increased on the 21st day by 341.08, 355.72, 499.85, 196.49, 187.48, and 363.35%. However, the PLT number decreased by 66.37, 69.46, 81.27, 49.24, 50.47, and 72.61%; hemoglobin content decreased by 39.02, 41.05, 60.52, 14.01, 17.20, and 42.36%. |
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References: [1]: Li C, Zheng X, Han Y, Lv Y, Lan F, Zhao J. XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway. Oncol Lett. (2018) 15:8973-82. doi: 10.3892/ol.2018.8491 |
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| Cas No. | 284028-89-3 | SDF | |
| 别名 | 3,5,7,8-四氢-2-[4-(三氟甲基)苯基]-4H-噻喃并[4,3-D]嘧啶-4-酮 | ||
| 化学名 | 2-[4-(trifluoromethyl)phenyl]-1,5,7,8-tetrahydrothiopyrano[4,3-d]pyrimidin-4-one | ||
| Canonical SMILES | C1CSCC2=C1NC(=NC2=O)C3=CC=C(C=C3)C(F)(F)F | ||
| 分子式 | C14H11F3N2OS | 分子量 | 312.31 |
| 溶解度 | ≥ 15.62mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 | 1.601 mL | 3.2019 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.50%
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