AGK 2 is a potent and selective inhibitor of sirtuin 2 with IC50 value of 3.5 μM .
Sirtuin 2 (SIRT2) is a NAD-dependent deacetylase and is involved in cell cycle regulation through α-tubulin deacetylation. SIRT2 plays an important role in neuroprotective effects and the pathogenesis and development of cancer   .
AGK 2 is a potent and selective SIRT2 inhibitor. AGK 2 inhibited SIRT2 with IC50 value of 3.5 μM and slightly inhibited SIRT1 and 3 at concentrations over 40 μM. AGK 2 increased acetylation of tubulin heterodimers from bovine brain. In HeLa cells expressing SIRT2-myc, AGK2 effectively inhibited SIRT2-myc activity. AGK2 also dose-dependently increased acetylated tubulin. In H4 cells transfected with α-Syn, AGK2 dose-dependently reduced α-Syn-mediated toxicity. In primary midbrain cultures transduced with lentivirus encoding α-SynA53T, AGK2 rescued dorsomedial neurons in a dose-dependent way . In primary rat astrocytes, AGK-2 (35 μM) significantly inhibited astrocyte viability and proliferation and also inhibited astrocyte activation induced by beta amyloid 1-42 (Aβ 1-42). Also, AGK2 significantly inhibited the increase of iNOS and COX-2 induced by Aβ 1-42 . In glioblastoma multiforme cancer stem cells (GBM CSCs), AGK-2 exhibited good antiproliferative activity .
. Outeiro TF, Kontopoulos E, Altmann SM, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science, 2007, 317(5837): 516-519.
. Scuderi C, Stecca C, Bronzuoli MR, et al. Sirtuin modulators control reactive gliosis in an in vitro model of Alzheimer's disease. Front Pharmacol, 2014, 5: 89.
. Rotili D, Tarantino D, Nebbioso A, et al. Discovery of salermide-related sirtuin inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer stem cells. J Med Chem, 2012, 55(24): 10937-10947.
|Physical Appearance||A solid|
|Storage||Store at -20°C|
|Solubility||≥9.3mg/mL in DMSO|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|