Tenovin-6
目录号 : GC16436
A small molecule activator of p53
Cas No.:1011557-82-6
Sample solution is provided at 25 µL, 10mM.
Tenovin-6 is an analog of tenovin-1 with more water-soluble and it inhibits the protein deacetylase activities of SIRT1, SIRT2 and SIRT3 with IC50 value of 21 μM, 10 μM, and 67 μM, respectively [1].
It has been identified that the cytotoxic effects of tenovin-6 may occur through the dysregulation of autophagy rather than induction of apoptosis in chronic lymphocytic leukemia cells. Sir2p homologs could be targets for tenovin-6 in mammalian cells.
Tenovin-6 decreases purified human SirT1 peptide deacetylase activity in vitro with an IC50 of 21 mM and human SirT2 activity with an IC50 of 10 mM. Inhibition of SirT3 by tenovin-6 in this assay was significantly lower with an IC50 of 67 mM. And the activity of HDAC8 is poorly inhibited by tenovin-6 with an IC50 above the highest concentration of 90 mM. In xenograft models, tenovins induce apoptosis in malignant cell lines, containing those derived from lympho-reticular neoplasia and decrease human tumor growth. Anti-leukaemic properties of Sirtuin inhibitors have also been demonstrated in recent pre-clinical studies on Tenovin in chronic myeloid leukaemia and Nicotinamide in CLL15 associated with increased p53-pathway function [1, 2].
Tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Interestingly, tenovin-6 induced apoptosis in the cell lines, those with wild-type TP53, mutant-type and null versions, which were accompanied by up regulation of death receptor 5. In the KatoIII cell line ( TP53-null), death receptor 5 silencing markedly attenuated tenovin-6-induced apoptosis, indicating that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Tenovin-6 combined with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells [3].
References:
[1]. Lain S, Hollick JJ, Campbell J, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell, 2008, 13(5): 454-463.
[2]. MacCallum SF, Groves MJ, James J, et al. Dysregulation of autophagy in chronic lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6. Scientific Reports, 2013, 3: 1275.
[3]. Hirai S, Endo S, Saito R, et al. Antitumor Effects Of A Sirtuin Inhibitor, Tenovin-6, Against Gastric Cancer Cells Via Death Receptor 5 Up-Regulation. PLoS ONE, 2014, 9(7): e102831.
| Kinase experiment [1]: | |
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In vitro deacetylation assays |
Assays were carried out using purified components in the Fluor de Lys Fluorescent Assay Systems. Relevant FdL substrates were used at 7 mM and NAD+ was used at 1 mM. Tenovin-6 was solubilized in DMSO with the final DMSO concentration in the reaction being less than 0.25%. For SirT1 and HDAC8, 1 unit of enzyme was used for each reaction, and for SirT2 and SirT3, 5 units were used for each reaction. Reactions were carried out at 37 °C for 1 hr. |
| Cell experiment [2]: | |
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Cell lines |
CLL 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 |
1, 5 or 10 μM; 8 or 24 hrs |
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Applications |
After 24-hr culture, Tenovin-6 showed a significant dose-dependent cytotoxic effect to CLL cells. In CLL cells treated with Tenovin-6 (10 μM) for 8 hrs, the metabolic activity reduced substantially, which was similar to the effects of Fludarabine (3 μM). |
| Animal experiment [1]: | |
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Animal models |
Female SCID mice bearing ARN8 melanomas |
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Dosage form |
50 mg/kg/day; i.p. |
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Applications |
In female SCID mice bearing ARN8 melanomas, Tenovin-6 significantly reduced tumor growth (day 6, p = 0.045; day 11, p = 0.0179; days 13 and 15, p = 0.0247). |
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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]. Lain S, Hollick JJ, Campbell J, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell, 2008, 13(5): 454-463. [2]. MacCallum SF, Groves MJ, James J, et al. Dysregulation of autophagy in chronic lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6. Scientific Reports, 2013, 3: 1275. | |
| Cas No. | 1011557-82-6 | SDF | |
| 化学名 | 4-tert-butyl-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide | ||
| Canonical SMILES | CC(C)(C)C1=CC=C(C=C1)C(=O)NC(=S)NC2=CC=C(C=C2)NC(=O)CCCCN(C)C | ||
| 分子式 | C25H34N4O2S | 分子量 | 454.6 |
| 溶解度 | ≥ 22.75mg/mL in DMSO, ≥ 2.62 mg/mL in EtOH with ultrasonic | 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 | 2.1997 mL | 10.9987 mL | 21.9974 mL |
| 5 mM | 0.4399 mL | 2.1997 mL | 4.3995 mL |
| 10 mM | 0.22 mL | 1.0999 mL | 2.1997 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
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet