Tenovin-6 Hydrochloride, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 Hydrochloride 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 Hydrochloride also inhibits dihydroorotate dehydrogenase (DHODH)^[1][2].

Tenovin-6 Hydrochloride 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 Hydrochloride rapidly increases the levels of endogenous K382-Ac p53 in MCF-7 cells^[1].
Tenovin-6 Hydrochloride (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 Hydrochloride 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 Hydrochloride 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 Hydrochloride inhibits autophagy does not correlate with p53 activation and SIRT1/2 inhibition by knockdown or knockout cannot mimic the effect of Tenovin-6 Hydrochloride on LC3B accumulation^[3].
Tenovin-6 Hydrochloride (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 Hydrochloride 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 Hydrochloride induces apoptosis through the extrinsic cell-death pathway^[4.
Tenovin-6 Hydrochloride 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

491.09

C₂₅H₃₅ClN₄O₂S

1011301-29-3

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

In Vitro: 

DMSO : ≥ 49 mg/mL (99.78 mM)

* “≥” means soluble, but saturation unknown.

*

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, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-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。

• [1]. Lain S, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008 May;13(5):454-63.

  [2]. Ladds MJGW, et al. Exploitation of DHODH and p53 activation as therapeutic targets – a case study in polypharmacology [published online ahead of print, 2020 Sep 8]. J Biol Chem. 2020;jbc.RA119.012056.

  [3]. Dai W, et al. Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma. Sci Rep. 2016 Mar 4;6:22622.

  [4]. Yuan H, et al. Tenovin-6 impairs autophagy by inhibiting autophagic flux. Cell Death Dis. 2017 Feb 9;8(2):e2608.

  [5]. Yuan H, et al. Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy. Oncotarget. 2017 Feb 28;8(9):14912-14924.

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Lain S, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008 May;13(5):454-63.

  [2]. Ladds MJGW, et al. Exploitation of DHODH and p53 activation as therapeutic targets – a case study in polypharmacology [published online ahead of print, 2020 Sep 8]. J Biol Chem. 2020;jbc.RA119.012056.

  [3]. Dai W, et al. Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma. Sci Rep. 2016 Mar 4;6:22622.

  [4]. Yuan H, et al. Tenovin-6 impairs autophagy by inhibiting autophagic flux. Cell Death Dis. 2017 Feb 9;8(2):e2608.

  [5]. Yuan H, et al. Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy. Oncotarget. 2017 Feb 28;8(9):14912-14924.