生物活性

• 靶点

  Sirtuin 1 IC50:131μM

  Sirtuin 2 IC50:38μM

• 描述Sirtinol is a class III HDAC (Sirt1 and Sirt2) inhibitor with IC50 values of 38μM (measured by purified human hGST-SIRT2) and 131μM for Sirt2 and Sirt1, respectively, almost no activity on other HDACs. Treatment with sirtinol at concentration of 30μM and 120μM for 48h resulted a significant decrease in the growth and viability of all of the PCa cell lines while an increased acetylated FOXO1 in both the nuclear and cytosolic cellular fractions could be observed at 24h. Sirtinol at concentration of 100μM induced senescence-like growth arrest in MCF-7 and H1299 cells after 24-hour-treatment which may partially due to the impaired activation of Ras–MAPK pathway in response to EGF and IGF-I. Pretreatment with 3-20μM sirtinol 5 minutes before being activated with fMLF/CB could dose-dependently inhibited the activity of neutrophil elastase from human neutrophils in response to various stimulators. Intraperitoneal injection with sirtinol at dose of 2.5mg/kg or 5mg/kg significantly inhibited HNE-induced paw edema in mice. Also it attenuated the MAO activity (a marker of neutrophil infiltration) as well as reduced pulmonary wet/dry weight ratio in the LPS-induced ALI mouse model at dose of 5mg/kg.

• 动物研究
  剂量	Mice: 1 mg/kg[3] (i.p.), 10 mg/kg[4] (i.p.), 0.1 mg/kg - 0.5 mg/kg[5] (i.p.) Rat: 1 mg/kg[6] (i.v.); 10 mg/kg[7] (i.p.)
  给药途径	i.p., i.v.