UBCS039

UBCS039 is the first synthetic, specific Sirtuin 6 (SIRT6) activator, inducing autophagy in human tumor cells, with an EC50 of 38 μM[1].

UBCS039, the first synthetic SIRT6 activator with EC50 of 38 μM, induces time-dependent activation of autophagy in multiple human tumor cell lines.

UBCS039 (75 μM, 48 or 72 hours) induces deacetylation of SIRT6-targeted histone H3 sites in human cancer cells. It leads to autophagosome accumulation in human cancer cells.UBCS039 induces autophagy via AMP-activated protein kinase (AMPK) signaling pathway activation.

Western Blot Analysis

Cell Line:	Human H1299 cells.
Concentration:	75 μM.
Incubation Time:	48 and 72 hours.
Result:	Induced deacetylation of SIRT6-targeted histone H3 sites in human H1299 cells.

Cell Proliferation Assay

Cell Line:	Human H1299 cells.
Concentration:	100 μM.
Incubation Time:	48 and 72 hours.
Result:	Led to a strong decrease of cell proliferation in a dose-dependent manner when compared with control or DMSO-treated cells, starting from day 3 of growth (48 h after treatment) in both H1299 and HeLa cell lines.

             

SIRT6: 38 μM (EC₅₀)

[1] Weijie You, et al. Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules. Angew. Chem. Int. Ed. 2017, 56, 1007-1011.
[2] Sara Iachettini, et al. Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells. Cell Death and Disease (2018) 9:996. DOI:10.1038/s41419-018-1065-0