规格 | 价格 | 库存 | 数量 |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Other Sizes |
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靶点 |
TNKS2: 2 nM (IC50)
TNKS1: 5 nM (IC50) ARTD2: 479 nM (IC50) ARTD1: 5500 nM (IC50) |
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体外研究 (In Vitro) |
XAV-939 针对 TNKS1 和 TNKS2 的 IC50 值分别为 5 nM 和 2 nM[1]。 XAV-939 (0.3–30 μM) 持续三天或十天可改善 hBMSC 的成骨细胞发育 [2]。通过引起 SH3BP2 积累,XAV-939 (3 μM) 刺激 hMSC 的成骨细胞分化 [2]。在成骨细胞发育过程中,XAV-939(3 μM;10 天)会增加 hBMSC 细胞中 OPG 的表达并降低 RANKL 的表达 [2]。 XAV-939 刺激 SFRP3 和 SFRP4 的产生,同时抑制 Wnt/β-连环蛋白信号传导 [3]。
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体内研究 (In Vivo) |
在体内,XAV-939 可恢复机械应力引起的软骨退化 [3]。
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酶活实验 |
抑制剂的筛选和抑制剂效力的测量[1]
通过搜索商业上可获得的化合物库来鉴定仅具有一个取代的黄酮衍生物,并通过Molport从不同的供应商处购买。将化合物储存在−20°C的二甲基亚砜中,并在TNKS1测定缓冲液中稀释,然后将其加入反应混合物中。在10μM和1μM下对化合物进行重复测试。在该筛选中使用化合物对照以排除化合物荧光和猝灭的影响。基于两点初始筛选,测量IC50值低于10μM的抑制剂的抑制能力。使用半对数稀释液测量IC50值,并对TNKS1进行一式四份的三次单独反应。调节孵育时间,使得底物转化率在筛选的情况下大于50%,在IC50测量的情况下小于30%。使用Graphpad Prism(Windows版本5.0)使用四个参数拟合剂量-反应曲线。 抑制剂的选择性[1] 使用上述同质活性测定法,还针对其他六个人类ARTD家族成员对鉴定的最佳坦激酶抑制剂进行了分析。基于先前进行的优化,每种酶的培养时间和条件各不相同。在分析测定中,底物NAD+浓度为250或500nM。为了获得稳健的信号,调节孵育时间,使得底物转化率在每种情况下都超过50%。为了有效地评估化合物的选择性,在1μM下对它们进行了表征。DMSO、化合物和蛋白质对照与所有酶一起使用,以排除或校正DMSO、自发荧光和荧光猝灭的影响。 |
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细胞实验 |
细胞活力测定[2]
细胞类型: hMSC-TERT 细胞系 测试浓度: 0.3、3 和 30 μM 孵育时间:3天 实验结果:证明0.3和3μM剂量对第1、2、3天的增殖没有显着影响,但在当天抑制hMSCs细胞增殖3 剂量为 30 μM。 细胞凋亡分析[2] 细胞类型: hMSC-TERT 细胞系 测试浓度: 3 μM 孵育时间: 3 天 实验结果: 在 XAV-939 处理的 hBMSC RT-PCR 中显示细胞死亡(凋亡和坏死)的微小百分比[2] 细胞类型: hMSC-TERT 细胞系 测试浓度: 3 µM 孵育时间: 10 天 <实验结果:成骨细胞相关基因标记物的基因表达上调,包括:ALP、COL1A1、RUNX2 和 OC。 |
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动物实验 |
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参考文献 |
[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. |
分子式 |
C14H11F3N2OS
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分子量 |
312.31
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精确质量 |
312.05441
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元素分析 |
C, 53.84; H, 3.55; F, 18.25; N, 8.97; O, 5.12; S, 10.27
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CAS号 |
284028-89-3
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相关CAS号 |
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外观&性状 |
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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化学名 |
2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[4,3-d]pyrimidin-4(5H)-one
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别名 |
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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运输条件 |
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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溶解度 (体外) |
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溶解度 (体内) |
Solubility in Formulation 1: 1.56 mg/mL (5.00 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.6 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1.56 mg/mL (5.00 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.6 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: 1.56 mg/mL (5.00 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Solubility in Formulation 4: Solubility in Formulation 1: ~1.6 mg/mL (5.0 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + + 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). Solubility in Formulation 6: 5 mg/mL (16.01 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 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 |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
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 ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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