Tenovin-6 Hydrochloride

SKU: orb1220070

Description

Tenovin-6 Hydrochloride is an SIRT1, SIRT2 and HDAC8 inhibitor(IC50s of 21 μM, 10 μM, and 67 μM for SirT1, SirT2, and SirT3, respectively), and is also a potent p53 activator .Inhibition of SIRT1/2 by Tenovin-6 induced apoptosis in UM cells by activating the expression of tumor suppressor genes such as p53 and elevating reactive oxygen species (ROS). Tenovin-6 inhibited the growth of UM cells. Tenovin-6 and vinblastine was synergistic in inducing apoptosis of UM cell line 92.1 and Mel 270. Furthermore, Tenovin-6 eliminated cancer stem cells in 92.1 and Mel 270 cells. In conclusion, our findings suggest that Tenovin-6 may be a promising agent to kill UM bulk tumor cells and CSCs.tenovin-6 increases microtubule-associated protein 1 light chain 3 (LC3-II) level in diverse cell types in a time- and dose-dependent manner. Mechanistically, the increase of LC3-II by tenovin-6 is caused by inhibition of the classical autophagy pathway via impairing lysosomal function without affecting the fusion between autophagosomes and lysosomes.tenovin-6 activation of p53 is cell type dependent, and tenovin-6 inhibition of autophagy is not dependent on its regulatory functions on p53 and SIRT1.

Images & Validation

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Key Properties

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CAS Number	1011301-29-3
MW	491.09
Purity	>98% (HPLC)
Formula	C₂₅H₃₅ClN₄O₂S
SMILES	Cl.CN(C)CCCCC(=O)NC1=CC=C(NC(=S)NC(=O)C2=CC=C(C=C2)C(C)(C)C)C=C1
Target	Sirtuin
Solubility	DMSO:45 mg/mL (91.63 mM)

Bioactivity

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In Vivo

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

In Vitro

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. 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. 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.

Storage & Handling

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Storage	Storage temperature: -20°C. Stability: ≥ 2 years
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

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Sirtuin

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