Sirtinol is a specific NAD-dependant class III histone deacetylase sirtuin inhibitor targeting human Sirt1 and Sirt2 with IC50 of 131 μM and 38 μM, respectively. Sirtinol is slightly less potent against recombinant yeast Sir2p with IC50 of 68 μM. Sirtinol does not affect HDAC1 activity at 50 μM, suggesting that it specifically inhibits sirtuin deacetylase activity. Unlike TSA, Sirtinol treatment does not cause HeLa cells to change from a rounded morphology to a flattened morphology. Consistently, TSA causes robust acetylation of histones H3 and H4, as well as α-tubulin, whereas Sirtinol does not produce any of these effects. Treatment with Sirtinol inhibits body-axis formation and vascularization in Arabidopsis. Although Sirtinol (100 μM) has no axonal toxicity on uninjured axons, it effectively blocks NAD-dependent axonal protection (NDAP) after transection, indicating that Sirt1 proteins are likely effectors of this process. Sirtinol significantly increases mononucleosomes and oligonucleosomes in the cytoplasm of cardiac myocytes, a sensitive marker of apoptosis, and induces cleavage of caspase-3 almost equally as H2O2.  Sirtinol induces senescence-like growth arrest in human breast cancer MCF-7 cells and lung cancer H1299 cells, characterized by induction of senescence-associated β-galactosidase activity and increased expression of plasminogen activator inhibitor 1 Sirtinol-induced senescence-like growth arrest is accompanied by impaired activation of Ras-MAPK pathways but not Akt/PKB in response to epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). Similar to Nicotinamide, Sirtinol inhibits the growth of MiaPaAa-2, BxPC-3, SOJ-6, and HeLa cells with IC50 of 48.1 μM, 48.5 μM, 48.4 μM, 53.9 μM, respectively.
|Cell lines||LNCaP, 22Rv1, DU145, and PC3|
|Preparation method||Growing cell to 60% confluence and then treating them with 30 μM or 120 μM sirtinol for 24 or 48 hours. Cells are trypsinized and collected. The cells are pelleted by centrifugation and resuspended in PBS (120 μL). Adding trypan blue (0.4% in PBS; 10 μL) to a smaller aliquot (10 μL) of cell suspension, and the number of cells (viable unstained and nonviable blue) are counted.|
|Concentrations||Dissolved in DMSO, final concentrations ~120 μM|
|Incubation time||24 or 48 hours|
|Animal models||Male Sprague-Dawley rats subjected to trauma-hemorrhage|
|Formulation||Dissolved in DMSO, and diluted in saline|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 11 mg/mL|
|Related Sirtuin Products|
SRT2183 is a selective activator of Sirtuin-1 (SIRT1) with EC1.5 value of 0.36 μM.
UBCS039 is an synthetic SIRT6 activator, with EC50 of 38 μM.
|Nicotinamide Riboside Chloride
Nicotinamide Riboside Chloride is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+.
SirReal2 is a potent and selective Sirt2 inhibitor with IC50 of 140 nM.
SRT2104 is a selective brain-permeable activator of SIRT1.
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