Tenovin-6, an analog of Tenovin-1, 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].
体内研究
Administered at 50 mg/kg intraperitoneally, it effectively inhibits tumor growth in mice[1].
体外研究
Tenovin-6 inhibits S. cerevisiae growth at an IC50 of 30 μM, showcasing greater toxicity to yeast compared to the less water-soluble Tenovin-1. Tenovin-6 notably elevates endogenous K382-Ac p53 levels in MCF-7 cells rapidly[1].
Tenovin-6, across a range of concentrations from 0 to 15 μM, dose-dependently elevates the level of LC3-II in various cell types, with this increase being dependent on ATG5/7. This treatment not only augments the quantity and brightness of autophagic vesicles, regardless of Torin 1 presence, but also blocks the Torin 1-induced degradation of SQSTM1/p62[3].
When applied at doses between 0, 1, 2.5, 5, and 10 μM, Tenovin-6 significantly curtails cell proliferation in a dose- and time-specific manner across OCI-Ly1, DHL-10, U2932, RIVA, HBL1, and OCI-Ly10 cell lines. It notably boosts the level of LC3B-II in DLBCL cell lines by obstructing the classical autophagy pathway, independently of SIRT1/2/3 and p53 activities, and propels apoptosis via the extrinsic cell-death pathway[4]. Furthermore, Tenovin-6 curbs the growth of UM cells, displaying IC50 values of 12.8 μM, 11.0 μM, 14.58 μM, and 9.62 μM for the 92.1, Mel 270, Omm 1, and Omm 2.3 cells, respectively[5].
搜索
