MDL 800 is an allosteric activator of sirtuin 6 (SIRT6).¹It selectively activates SIRT6 deacetylase activity over SIRT1-5 and -7 and histone deacetylase 1 (HDAC1) and HDAC2-11 deacetylase activity in cell-free assays at 100 µM. It induces histone deacetylation (IC₅₀= 23.3 µM) in, and reduces proliferation of, BEL-7405 hepatocellular carcinoma (HCC) cells (EC₅₀= 90.4 µM). MDL 800 (0.1-5 µM) inhibits TNF-α release induced by oxygen and glucose deprivation (OGD) in primary mouse microglia.²In vivo, MDL 800 (50, 100, and 150 mg/kg) reduces tumor weight and volume in a BEL-7405 HCC mouse xenograft model.¹

1.Huang, Z., Zhao, J., Deng, W., et al.Identification of a cellularly active SIRT6 allosteric activatorNat. Chem. Biol.14(12)1118-1126(2018) 2.He, T., Shang, J., Gao, C., et al.A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axisActa Pharm. Sin. B11(3)708-726(2021)