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Tenovin-6

现货
Catalog No.
A8302
SIRT抑制剂,p53激活剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 3,300.00
现货
1mg
¥ 1,050.00
现货
5mg
¥ 3,470.00
现货
10mg
¥ 4,280.00
现货
25mg
¥ 9,410.00
现货

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20° C
M.Wt454.6
Cas No.1011557-82-6
FormulaC25H34N4O2S
Solubility≥22.75mg/mL in DMSO, ≥2.62 mg/mL in EtOH with ultrasonic, <2.02 mg/mL in H2O
Chemical Name4-tert-butyl-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide
SDFDownload SDF
Canonical SMILESCC(C)(C)C1=CC=C(C=C1)C(=O)NC(=S)NC2=CC=C(C=C2)NC(=O)CCCCN(C)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

体外去乙酰化实验

在Fluor de Lys荧光测定系统中,使用纯化组分进行测定。使用7 mM FdL相关底物和1mM NAD+。将Tenovin-6溶于DMSO中,DMSO在反应中的最终浓度小于0.25%。对于SirT1和HDAC8,每个反应消耗1个单位的酶。对于SirT2和SirT3,每个反应消耗5个单位。反应在37 °C进行1小时。

细胞实验 [2]:

细胞系

CLL细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

1, 5或10 μM;8或24小时

实验结果

于培养24小时后,Tenovin-6呈剂量依赖性地显著抑制CLL细胞。在经过Tenovin-6 (10 μM) 处理8小时的CLL细胞中,细胞代谢活性显着降低。Tenovin-6 (10 μM) 与Fludarabine (3 μM) 具有相似的效果。

动物实验 [1]:

动物模型

携带ARN8黑色素瘤的雌性SCID小鼠

给药剂量

50 mg/kg/day;腹腔注射

实验结果

在携带ARN8黑色素瘤的雌性SCID小鼠中,Tenovin-6显著抑制肿瘤生长(第6天,p = 0.045;第11天,p = 0.0179;第13和15天,p = 0.0247)。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

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.

生物活性

Description Tenovin-6是沉默调节蛋白(sirtuin)的抑制剂,对SIRT1、SIRT2和SIRT3的IC50值分别为21 ?M、10 ?M和67 ?M。
靶点 SIRT1 SIRT2 SIRT3 p53    
IC50 21 ?M 10 ?M 67 ?M      

质量控制