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| 25mg |
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Purity: ≥98%
Tenovin-6 is an analog of tenovin-1 that is more water-soluble and may have anticancer properties. With IC50 values of 21 μM, 10 μM, and 67 μM, respectively, it works by inhibiting the protein deacetylase activities of SIRT1, SIRT2, and SIRT3. In contrast to inducing apoptosis in chronic lymphocytic leukemia cells, tenovin-6's cytotoxic effects are caused by the dysregulation of autophagy.
| Targets |
SIRT2 (IC50 = 10 μM); SIRT1 (IC50 = 21 μM); SIRT3 (IC50 = 67 μM); HDAC8; MDM-2/p53
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| ln Vitro |
Tenovin-6, which is more toxic to yeast than the less water-soluble tenovin-1, has an IC50 of 30 μM and inhibits the growth of S. cerevisiae cultures. In MCF-7 cells, tenovin-6 significantly raises endogenous K382-Ac p53 levels[1].
Tenovin-6 (0 to 15 μM) dose dependently increases the level of LC3-II in diverse cell types, and the increase is ATG5/7 dependent. Additionally, the use of tenovin-6 prevents SQSTM1/p62 degradation caused by torin 1 and boosts the quantity and intensity of autophagic vesicles both with and without torin 1. The fusion between autophagosomes and lysosomes is unaffected by tenovin-6, but it does affect the acidification of autolysosomes and the hydrolytic activity of lysosomes. Tenovin-6 inhibits autophagy but not p53 activation, and sirtuin 1 inhibition by knockdown or knockout cannot mimic tenovin-6's effect on LC3B accumulation[3]. Tenovin-6 (0, 1, 2.5, 5 or 10 μM) potently inhibits cell proliferation in all OCI-Ly1, DHL-10, U2932, RIVA, HBL1 and OCI-Ly10 cell lines in a dose- and time-dependent manner. Tenovin-6 consistently raises the level of LC3B-II in DLBCL cell lines by inhibiting the traditional autophagy pathway without activating p53, and the rise is unrelated to SIRT1/2/3 and p53. Through the extrinsic cell-death pathway, tenovin-6 causes apoptosis[4]. Tenovin-6 inhibits the growth of UM cells, with IC50 values for 92.1, Mel 270, Omm 1 and Omm 2.3 cells of 12.8 μM, 11.0 μM, 14.58 μM and 9.62 μM, respectively[5]. |
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| ln Vivo |
Tenovin-6 (50 mg/kg, i.p.) prevents tumor growth in mice[1].
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| Enzyme Assay |
In the Fluor de Lys Fluorescent Assay Systems, assays are conducted using purified components. Utilized are NAD+ at 1 mM and pertinent FdL substrates at 7 μM. The final DMSO concentration in the reaction is less than 0.25%, and tenovins are thuslylubilized in DMSO. In comparison to SirT2 and SirT3, SirT1 and HDAC8 each require one unit of enzyme, while SirT2 and SirT3 require five units. One hour of reactions is conducted at 37°C.
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| Cell Assay |
The MTS assay is used to evaluate cell viability.
In 96-well plates, UM cells are seeded into each well (5,000 cells/well), treated the following day with control or Tenovin-6 in increasing concentrations from 0 to 20 μM for 68 h, and then MTS is added at 20 μL/well to be read at a wave length of 490 nm. The IC50 is calculated by curve fitting the sigmoidal dose-response curve.
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| Animal Protocol |
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| References |
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| Additional Infomation |
Tenovin-6 is a monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(dimethylamino)pentanoic acid with the aromatic amino group of N-[(4-aminophenyl)carbamothioyl]-4-tert-butylbenzamide. It has a role as an antineoplastic agent, a Sir2 inhibitor and a p53 activator. It is a monocarboxylic acid amide, a member of thioureas and a tertiary amino compound.
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| Molecular Formula |
C25H34N4O2S
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| Molecular Weight |
454.63
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| Exact Mass |
454.24
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| CAS # |
1011557-82-6
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| Related CAS # |
Tenovin-6 Hydrochloride;1011301-29-3
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| PubChem CID |
24772043
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| Appearance |
White to off-white solid
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.617
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| LogP |
3.64
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
616
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NC(NC1=CC=C(NC(CCCCN(C)C)=O)C=C1)=S)C2=CC=C(C(C)(C)C)C=C2
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| InChi Key |
BVJSXSQRIUSRCO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H34N4O2S/c1-25(2,3)19-11-9-18(10-12-19)23(31)28-24(32)27-21-15-13-20(14-16-21)26-22(30)8-6-7-17-29(4)5/h9-16H,6-8,17H2,1-5H3,(H,26,30)(H2,27,28,31,32)
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| Chemical Name |
4-tert-butyl-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide
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| Synonyms |
Tenovin-6; Tenovin6; Tenovin 6
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
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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| Solubility (In Vitro) |
DMSO: ~98 mg/mL (~215.6 mM)
Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: <1 mg/mL (slightly soluble or insoluble) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 add 100 μL of 25.0 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: ≥ 2.5 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 add 100 μL of 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1996 mL | 10.9980 mL | 21.9959 mL | |
| 5 mM | 0.4399 mL | 2.1996 mL | 4.3992 mL | |
| 10 mM | 0.2200 mL | 1.0998 mL | 2.1996 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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