[CAS NO. 1011557-82-6] Tenovin-6
PRODUCTS SPECIFICATIONS [1011557-82-6]
DESCRIPTION [1011557-82-6]
Overview
| MDL | MFCD11976906 |
|---|---|
| Molecular Weight | 454.63 |
| Molecular Formula | C25H34N4O2S |
| SMILES | O=C(NC(NC1=CC=C(NC(CCCCN(C)C)=O)C=C1)=S)C2=CC=C(C(C)(C)C)C=C2 |
4 Publications Citing Use of MCE
Summary
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 IC 50 s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH) [1] [2] .
IC50 & Target
|
SIRT2 10 μM (IC 50 ) |
SIRT1 21 μM (IC 50 ) |
SIRT3 67 μM (IC 50 ) |
HDAC8
|
MDM-2/p53
|
In Vitro
Tenovin-6 inhibits the growth of S. cerevisiae cultures with an IC
50
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.
Appearance
Solid
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
DMSO : ≥ 31 mg/mL ( 68.19 mM )
* "≥" means soluble, but saturation unknown.
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 |
-
1.
-
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
References
- [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.