2. Apoptosis
    Metabolic Enzyme/Protease
    Cell Cycle/DNA Damage
    Epigenetics
    Autophagy
  3. MDM-2/p53
    Dihydroorotate Dehydrogenase
    Sirtuin
    Autophagy
  4. Tenovin-6

Tenovin-6 

Cat. No.: HY-15510 Purity: 98.67%
COA Handling Instructions

Tenovin-6, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC50s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH).

For research use only. We do not sell to patients.

Tenovin-6 Chemical Structure

Tenovin-6 Chemical Structure

CAS No. : 1011557-82-6

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10 mM * 1 mL in DMSO USD 88 In-stock
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Customer Review

Based on 5 publication(s) in Google Scholar

Other Forms of Tenovin-6:

Top Publications Citing Use of Products

    Tenovin-6 purchased from MCE. Usage Cited in: J Nutr. 2020 Jul 1;150(7):1731-1737.  [Abstract]

    The cell viability in untreated SH-SY5Y cells or those stimulated with Tenovin-6 and then treated with MPP+ or the combination of MPP+ and CPO-A.

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    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Tenovin-6, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC50s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH)[1][2].

    IC50 & Target[1]

    SIRT2

    10 μM (IC50)

    SIRT1

    21 μM (IC50)

    SIRT3

    67 μM (IC50)

    HDAC8

     

    MDM-2/p53

     

    In Vitro

    Tenovin-6 inhibits the growth of S. cerevisiae cultures with an IC50 of 30 μM and is more toxic to yeast than the less water-soluble tenovin-1. Tenovin-6 rapidly increases the levels of endogenous K382-Ac p53 in MCF-7 cells[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. Tenovin-6 treatment also increases the number and intensity of autophagic vesicles with or without the presence of Torin 1, and prevents Torin 1-induced SQSTM1/p62 degradation. Tenovin-6 affects the acidification of autolysosomes and impairs the hydrolytic activity of lysosomes but does not affect the fusion between autophagosomes and lysosomes. That tenovin-6 inhibits autophagy does not correlate with p53 activation and SIRT1/2 inhibition by knockdown or knockout cannot mimic the effect of tenovin-6 on LC3B accumulation[3].
    Tenovin-6 (0, 1, 2.5, 5 or 10 μM) potently inhibits cell proliferation in a dose- and time-dependent manner in all OCI-Ly1, DHL-10, U2932, RIVA, HBL1 and OCI-Ly10 cell lines. Tenovin-6 consistently increases LC3B-II level in DLBCL cell lines by inhibiting the classical autophagy pathway, without activating p53, and the increase is independent of SIRT1/2/3 and p53. Tenovin-6 induces apoptosis through the extrinsic cell-death pathway[4.
    Tenovin-6 suppresses the growth of UM cells with IC50 of 12.8 μM, 11.0 μM, 14.58 μM and 9.62 μM for 92.1, Mel 270, Omm 1 and Omm 2.3 cells, respectively    [5].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    In Vivo

    Tenovin-6 (50 mg/kg, i.p.) inhibits the growth of tumor in mice[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Molecular Weight

    454.63

    Appearance

    Solid

    Formula

    C25H34N4O2S
    CAS No.
    SMILES

    O=C(NC(NC1=CC=C(NC(CCCCN(C)C)=O)C=C1)=S)C2=CC=C(C(C)(C)C)C=C2
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 31 mg/mL (68.19 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (5.50 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (5.50 mM); Clear solution

    *All of the co-solvents are available by MCE.
    Purity & Documentation
    References
    Kinase Assay
    [1]

    Assays are carried out using purified components in the Fluor de Lys Fluorescent Assay Systems. Relevant FdL substrates are used at 7 μM and NAD+ at 1 mM. Tenovins are solubilized in DMSO with the final DSMO concentration in the reaction being less than 0.25%. For SirT1 and HDAC8, one unit of enzyme is used per reaction, and for SirT2 and SirT3, five units is used per reaction. Reactions are carried out at 37°C for 1 hr.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Cell Assay
    [4]

    The MTS assay is used to evaluate cell viability. UM cells are seeded into each well of 96-well plates (5,000 cells/well) and treated the next day with control or Tenovin-6 in an 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 determined by curve fitting of the sigmoidal dose-response curve.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Female SCID mice are injected subcutaneously with 1×106 ARN8 cells suspended in matrigel. Tumors are allowed to reach a size of approximately 10 mm3. Tenovin-6 is administered daily at 50 mg/kg by intraperitoneal injection. Control animals are treated with vehicle solution containing cyclodextrin 20% (w/v) and DMSO 10% (v/v). Tumor diameters are measured using calipers, and volumes are calculated using the equation V=π4/3[(d1 + d2)/4]3. Median values of tumor size are calculated for each time point as well as the corresponding 95% confidence intervals. Comparison of control and drug-treated tumor size distributions are made by Mann-Whitney U-test. An alpha-level of 0.05 is considered appropriate for determination of statistical significance.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    References
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    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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    Keywords:

    Tenovin-61011557-82-6Tenovin6Tenovin 6MDM-2/p53Dihydroorotate DehydrogenaseSirtuinAutophagyDHODHMDM2protein-deacetylatingacetylationdegradationInhibitorinhibitorinhibit

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