Tenovin-6

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 IC₅₀s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH)^[1][2]. IC50 & Target: IC50: 21 μM (SirT1), 10 μM (SirT2), 67 μM (SirT3)^[1] 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^[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]. In Vivo: Tenovin-6 (50 mg/kg, i.p.) inhibits the growth of tumor in mice^[1].