生物活性

• 靶点

  Sirtuin 1 EC1.5:0.16μM

  Sirtuin 2 EC1.5:37μM

  Sirtuin 3 EC1.5:300μM

• 描述The maximum activation ratio of SRT1720 versus the closest sirtuin homologues, SIRT2 (EC1.5 = 37 μM) and SIRT3 (EC1.5 > 300 μM) is up to 781%. SRT1720 binds to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. SRT1720 could reduce fed glucose levels. Glucose excursion during an intraperitoneal glucose tolerance test is also significantly reduced in the SRT1720 group, and comparable to rosiglitazone, a PPARγ activator that has been used to treat type 2 diabetes. SRT1720 does not have an effect on fasting glucose in chow-fed mice, revealing that pharmacological SIRT1 activation is unlikely to induce hypoglycaemia. SRT1720 significantly reduces the hyperinsulinaemia after 4 weeks, partially normalizing increased insulin levels similar to rosiglitazone treatment. SRT1720 treatment increases mitochondrial capacity by 15% in gastrocnemius muscle as measured by citrate synthase activity. Higher concentrations of SRT1720 (15 μM) induces a modest (10-20%) decrease in normal cell viability. SRT1720 also significantly inhibits VEGF-dependent MM cell migration.

• 动物研究
  剂量	Rat: 5 mg/kg[3] (i.p.) Mice: 10 mg/kg - 100 mg/kg[2] (p.o.); Nude Mice: 50 mg/kg - 200 mg/kg[4] (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Mice[2] Dose 100 mg/kg Administration p.o. F 0.5 T1/2 ~ 5 h AUC 7892 ng/h/ml