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Tenovin 6 Hydrochloride

Cat. No. M6241
Tenovin 6 Hydrochloride Structure
Synonym:

Tenovin 2

Size Price Availability Quantity
10mM*1mL in DMSO USD 240  USD240 In stock
2mg USD 90  USD90 In stock
5mg USD 220  USD220 In stock
10mg USD 350  USD350 In stock
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Quality Control & Documentation
Biological Activity

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. 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. 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. 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.

In vivo: Tenovin-6 (50 mg/kg, i.p.) inhibits the growth of tumor in mice.

Protocol (for reference only)
Cell Experiment
Cell lines UM cells
Preparation method 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.
Concentrations 0 to 20 μM
Incubation time 68 h
Animal Experiment
Animal models SCID mice
Formulation cyclodextrin 20% (w/v) and DMSO 10% (v/v)
Dosages 50 mg/kg
Administration i.p.
Chemical Information
Molecular Weight 491.09
Formula C25H35ClN4O2S
CAS Number 1011301-29-3
Solubility (25°C) 49 mg/mL in DMSO
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Yuan H, et al. Cell Death Dis. Tenovin-6 impairs autophagy by inhibiting autophagic flux.

[2] Dai W, et al. Sci Rep. Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma.

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