SRT1720 HCl is an activator of SIRT1 (EC1.5 = 0.16 μM and maximum activation = 781%) [1], a NAD+-dependent protein and histone deacetylase that plays an important role in numerous biologic processes [2]. SRT1720 HCl also inhibited p300 activity with IC50 of 9 μM [3].
SRT1720 HCl treatment decreased the expression of lipogenic genes in HepG2 cells [4]. The viability of MDA-MB-231 and BT20 basal-type breast cancer cells decreased by more than 80% with 5 μM of SRT1720 HCl, whereas the viability of MCF-7 luminal-type cells only decreased by 20% with 20 μM of treatment. After SRT1720 HCl (5 μM, 8h) treatment, 1% of the MDA-MB-231 cells were positive for early apoptosis and 12% of the cells were positive for late apoptosis/necrosis [2].
SRT1720 HCl (200 mg/kg for 10 wk) reduced fat accumulation in the liver and ameliorated liver dysfunction in MSG mice. The administration of SRT1720 HCl to MSG mice for 10 wk reduced fat accumulation by 21%. The serum levels of aminotransferases were also elevated in MSG mice. Administration of SRT1720 HCl improved dyslipidemia in MSG mice [4]. Administration of SRT1720 HCl (100 mg/kg) reduced fed glucose levels after 1 week of treatment that continued through 10 weeks of dosing in diet-induced obesity (DIO) mice [5].
参考文献:
[1]. Milne J C, Lambert P D, Schenk S, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes[J]. Nature, 2007, 450(7170): 712-716.
[2]. Lahusen T J, Deng C X. SRT1720 Induces Lysosomal-Dependent Cell Death of Breast Cancer CellsSRT1720 Induces Lysosomal-Dependent Cell Death[J]. Molecular cancer therapeutics, 2015, 14(1): 183-192. SRT1720 treatment decreased the expression of lipogenic genes in HepG2 cells.
[3]. Huber J L, McBurney M W, DiStefano P S, et al. SIRT1-independent mechanisms of the putative sirtuin enzyme activators SRT1720 and SRT2183[J]. Future medicinal chemistry, 2010, 2(12): 1751-1759.
[4]. Yamazaki Y, Usui I, Kanatani Y, et al. Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice[J]. American Journal of Physiology-Endocrinology and Metabolism, 2009, 297(5): E1179-E1186.
SRT1720 HCl 是 SIRT1 的激活剂（EC1.5 = 0.16 µ；M 和最大激活 = 781%）[1]，一种 NAD+- 依赖性蛋白和组蛋白脱乙酰酶，在许多生物过程[2]。 SRT1720 HCl 也抑制 p300 活性，IC50 为 9 77777#181;M [3]。
SRT1720 HCl 处理降低 HepG2 细胞脂肪生成基因的表达[4]< /sup>。 MDA-MB-231 和 BT20 基底型乳腺癌细胞的生存力随着 5 77777#181;M 的 SRT1720 HCl 下降超过 80%，而 MCF-7 管腔型细胞的生存力仅下降 20% 与 20 μM 的治疗。 SRT1720 HCl (5 μM, 8h)处理后，1%的MDA-MB-231细胞呈早期凋亡阳性，12%的细胞呈晚期凋亡/坏死[2]。
SRT1720 HCl（200 mg/kg，持续 10 周）减少 MSG 小鼠肝脏中的脂肪堆积并改善肝功能障碍。对 MSG 小鼠施用 SRT1720 HCl 10 周后，脂肪堆积减少了 21%。 MSG 小鼠的转氨酶血清水平也升高。施用 SRT1720 HCl 可改善 MSG 小鼠的血脂异常[4]。 SRT1720 HCl (100 mg/kg) 在饮食诱导的肥胖 (DIO) 小鼠中持续给药 10 周后 1 周后降低了进食葡萄糖水平 [5]。
| Cell experiment [1]: | |
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Cell lines |
MDA-MB-231 Breast cancer cells, BT20 basal-type breast cancer cells, MCF-7 luminal-type cells |
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Preparation Method |
MDA-MB-231 cells were plated at 15,000 cells/well in 24-well plates. The day after plating, SRT1720 HCl was added to the cells for the designated time and concentration. Cell viability was assessed by methylthiazolydiphenyl-tetrazolium bromide (MTT) assay. |
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Reaction Conditions |
0-20μM for 24 hours |
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Applications |
The viability of MDA-MB-231 and BT20 basal-type breast cancer cells decreased by more than 80% with 5 μmol/L of SRT1720, whereas the viability of MCF-7 luminal-type cells only decreased by 20% with 20 μmol/L of treatment |
| Animal experiment [2]: | |
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Animal models |
male MSG mice and control male ICR mice |
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Preparation Method |
Twenty ICR mice and 12 MSG mice at 6 wk old were analyzed as pretreatment groups before starting SRT1720 HCl treatment. SRT1720 HCl was mixed with standard chow (200 mg.kg body wt-1.day-1) and orally administered to 6-wk-old MSG mice for 10 wk. Fifteen ICR mice, 15 MSG mice, and 15 MSG mice with SRT1720 HCl treatment at 16 wk old were analyzed as post treatment groups after a 10-wk treatment period. |
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Dosage form |
200 mg.kg body wt-1.day-1, oral |
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Applications |
Administration of SRT1720 HCl reduced the acetylation level of PGC-1α almost to the control level, whereas it did not alter the expression of SIRT1 at either the mRNA or protein levels in the liver. The body weight and the weight of the epididymal fat in 16-wk-old MSG mice was higher than those in control mice by ～20 and 60%, respectively. SRT1720 HCl treatment did not significantly affect the body weight or food intake of the MSG mice. |
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参考文献: [1]: Lahusen T J, Deng C X. SRT1720 Induces Lysosomal-Dependent Cell Death of Breast Cancer CellsSRT1720 Induces Lysosomal-Dependent Cell Death[J]. Molecular cancer therapeutics, 2015, 14(1): 183-192. |
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