Sirtinol is a selective SIRT1/2 inhibitor (IC50: 131/38 μM).

SIRT1:131 μM, SIRT2:38 μM

在雄性SD大鼠中,Sirtinol（1 mg/kg）可减弱促炎性细胞因子的释放并保护创伤后出血.

在MCF-7和H1299细胞中,Sirtinol（100 μM）处理24小时可造成持续性的生长抑制直至第9天撤走Sirtinol。Sirtinol可诱导MCF-7和H1299细胞SA-β-gal 活性升高和PAI-1表达,且比Splitomicin效果更好。在MCF-7和H1299细胞中,Sirtinol（>33 μM）抑制克隆形成的效果强于Splitomicin。Sirtinol（100 μM）可使MCF-7 和 H1299细胞中本底的和EGF或IGF-I诱导产生的ERK、JNK/SAPK和p38 MAPK磷酸化水平显著减少。Sirtinol可阻断本底的和EGF诱导的Ras活性。与其一致,Sirtinol处理的细胞中,本底的和IGF-I或EGF诱导产生的MEK,Raf-1,MKK7和SEK1/MKK4磷酸化降低。Sirtinol可有效抑制体外酵母重组Sir2p的酶活性（IC50：68 μM）。与TSA不同,Sirtinol对人源的HDAC1无抑制效果,这表明Sirtinol也许是一种sirtuin家族特异性的抑制剂。且在人的初始成纤维细胞中,Sirtinol不引起组蛋白和微管蛋白整体乙酰化水平的变化,也不会使HeLa肿瘤细胞系形态发生变化。Sirtinol可抑制Sirt1活性从而增加UV和H2O2诱导的p53乙酰化从而加速皮肤角质细胞的凋亡。Sirt1的酶活被Sirtinol处理阻断后,显著抑制人源PCa细胞的生长和成活力,但不影响普通前列腺上皮细胞。

Inhibition in vitro of human Sirt2 activity: 1.5 μg of recombinant human GST-Sirt2 (amino acids 18-340) are incubated at 30°C for 2 hours in 50 μL of assay buffer (50 mM Tris-HCl, pH 8.8, 4 mM MgCl2, 0.2 mM dithiothreitol with different concentrations of Sirtinol, 50 μM NAD, and tritiated acetylated HeLa histones (1000 cpm), purified by acid extraction. HDAC activity is determined by scintillation counting of the ethyl acetate-soluble [3H]acetic acid.

Cells are grown to 60% confluence and then treated 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). Trypan blue (0.4% in PBS; 10 μL) is added to a smaller aliquot (10 μL) of cell suspension, and the number of cells (viable unstained and nonviable blue) are counted. (Only for Reference)