Tenovin-6 Hydrochloride, an analog of Tenovin-1 , is an activator of p53 transcriptional activity. Tenovin-6 Hydrochloride 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 Hydrochloride also inhibits dihydroorotate dehydrogenase (DHODH)
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. 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Tenovin-6 Hydrochloride (50 mg/kg, i.p.) inhibits the growth of tumor in mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:SIRT2 10 μM (IC 50 ) SIRT1 21 μM (IC 50 ) SIRT3 67 μM (IC 50 ) HDAC8 MDM-2/p53
