SRT1720 HCl

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].

References:
[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 µ ;M 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]。