Tenovin-6 |
| رقم الكتالوجGC16436 |
Tenovin-6 ، نظير Tenovin-1 ، هو منشط لنشاط النسخ p53يثبط Tenovin-6 أنشطة بروتين ديسيتيلاز للإنسان المنقى SIRT1 و SIRT2 و SIRT3 مع IC50s من 21 ميكرومتر و 10 ميكرومتر و 67 ميكرومتر ، على التوالييثبط Tenovin-6 أيضًا نازعة هيدروجين ثنائي هيدروجين (DHODH)
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Chemical Name | 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 | ||
| Formula | C25H34N4O2S | M.Wt | 454.6 |
| الذوبان | ≥ 22.75mg/mL in DMSO, ≥ 2.62 mg/mL in EtOH with ultrasonic | Storage | Store at -20° C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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