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.
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. |
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 |
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.
[1] Yuan H, et al. Cell Death Dis. Tenovin-6 impairs autophagy by inhibiting autophagic flux.
Related Sirtuin Products |
---|
ADTL-SA1215
ADTL-SA1215 is a first-in-class, specific small molecule activator of SIRT3 that modulates autophagy in triple-negative breast cancer. |
SIRT2/6-IN-1
SIRT2/6-IN-1 is a SIRT6/SIRT2 inhibitor, with IC50s of 106 μM and 114 μM. |
SIRT6-IN-2
SIRT6-IN-2 is a selective SIRT6 inhibitor (IC50: 34 μM). |
SIRT6-IN-3
SIRT6-IN-3 is a selective inhibitor of SIRT6 (IC50=7.49 μM). |
Z26395438
Z26395438 is a potent Sirtuin-1 inhibitor, with an IC50 value of 1.6 μM. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.