(S)-2-(trimethylsilyl)ethyl-3-(tert-butyldimethylsilyloxy)-7-(octanoylthio)hept-4-enoate | 1217362-00-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-2-(trimethylsilyl)ethyl-3-(tert-butyldimethylsilyloxy)-7-(octanoylthio)hept-4-enoate
• 英文别名: 2-trimethylsilylethyl (E,3S)-3-[tert-butyl(dimethyl)silyl]oxy-7-octanoylsulfanylhept-4-enoate
• CAS: 1217362-00-9
• 化学式: C₂₆H₅₂O₄SSi₂
• 分子量: 516.933
• InChiKey: DWKOYGSYBCCRDZ-CZTSOZTGSA-N

物化性质

• 沸点：
  514.7±50.0 °C(Predicted)
• 密度：
  0.949±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.21
• 重原子数：
  33
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  77.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-(trimethylsilyl)ethyl-3-(tert-butyldimethylsilyloxy)-7-(octanoylthio)hept-4-enoate 在 哌啶 、 N-羟基-7-氮杂苯并三氮唑 、 2-[[三(羟甲基)甲基]氨基]乙磺酸 、 左旋樟脑磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.33h， 生成 largazole
  参考文献：
  名称：

  Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells

  摘要：

  Aberration in cell cycle has been shown to be a common occurrence in lung cancer, and cell cycle inhibitor represents an effective therapeutic strategy. In this study, we test the effects of a natural macrocyclic depsipeptide largazole on lung cancer cells and report that this compound potently inhibits the proliferation and clonogenic activity of lung cancer cells but not normal bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up-regulation of the expression of cyclin-dependent kinase inhibitor p21. Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a proteasomal degradation of E2F1, leading to suppression of E2F1 function in lung cancer but not normal bronchial epithelial cells. Because E2F1 is overexpressed in lung cancer tumor samples, these data indicate that largazole is an E2F1-targeting cell cycle inhibitor, which bears therapeutic potentials for this malignant neoplasm.

  DOI：

  10.1021/ml400093y
• 作为产物：
  描述：

  2-trimethylsilylethyl (3S)-3-[tert-butyl(dimethyl)silyl]oxy-7-hydroxyhept-4-enoate 在 1-octanesulfinic acid 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-2-(trimethylsilyl)ethyl-3-(tert-butyldimethylsilyloxy)-7-(octanoylthio)hept-4-enoate
  参考文献：
  名称：

  Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells

  摘要：

  Aberration in cell cycle has been shown to be a common occurrence in lung cancer, and cell cycle inhibitor represents an effective therapeutic strategy. In this study, we test the effects of a natural macrocyclic depsipeptide largazole on lung cancer cells and report that this compound potently inhibits the proliferation and clonogenic activity of lung cancer cells but not normal bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up-regulation of the expression of cyclin-dependent kinase inhibitor p21. Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a proteasomal degradation of E2F1, leading to suppression of E2F1 function in lung cancer but not normal bronchial epithelial cells. Because E2F1 is overexpressed in lung cancer tumor samples, these data indicate that largazole is an E2F1-targeting cell cycle inhibitor, which bears therapeutic potentials for this malignant neoplasm.

  DOI：

  10.1021/ml400093y

文献信息

• Discovery of Novel Class I Histone Deacetylase Inhibitors with Promising in Vitro and in Vivo Antitumor Activities
  作者：Yiwu Yao、Zhengchao Tu、Chenzhong Liao、Zhen Wang、Shang Li、Hequan Yao、Zheng Li、Sheng Jiang

  DOI：10.1021/acs.jmedchem.5b01044

  日期：2015.10.8

  exhibit promising antiproliferative activities in the nanomolar range against various cancer cell lines. Compounds 12 and 13 show more than 20-fold selectivity toward human cancer cells over human normal cells in comparison with romidepsin (FK228), demonstrating low probability of toxic side effects. In addition, compound 13 exhibits excellent in vivo anticancer activities in a human prostate carcinoma (Du145)

  描述了一种成功的基于环状结构的新型环状二肽，其选择性靶向I类HDAC同工型。化合物11具有2.78 nM的IC 50，可与HDAC1蛋白结合，并且前药12和13在纳摩尔范围内还具有针对各种癌细胞系的有希望的抗增殖活性。与罗米地辛（FK228）相比，化合物12和13对人癌细胞的选择性超过人正常细胞的20倍以上，这表明毒性副作用的可能性较低。另外，化合物13在人前列腺癌（Du145）异种移植模型中显示出优异的体内抗癌活性，没有观察到毒性。因此，前药13具有作为用于进一步临床翻译的新型抗癌剂的治疗潜力。
• 10.1021/01100308a
  作者：Zeng, Xin、Yin, Biaolin、Hu, Zheng、Liao, Chenzhong、Liu, Jinglei、Li, Shang、Li, Zheng、Nicklaus, Marc C.、Zhou, Guangbiao、Jiang, Sheng

  DOI：10.1021/01100308a

  日期：——
• Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells
  作者：Li-Chuan Wu、Zhe-Sheng Wen、Ya-Tao Qiu、Xiao-Qin Chen、Hao-Bin Chen、Ming-Ming Wei、Zi Liu、Sheng Jiang、Guang-Biao Zhou

  DOI：10.1021/ml400093y

  日期：2013.10.10

  Aberration in cell cycle has been shown to be a common occurrence in lung cancer, and cell cycle inhibitor represents an effective therapeutic strategy. In this study, we test the effects of a natural macrocyclic depsipeptide largazole on lung cancer cells and report that this compound potently inhibits the proliferation and clonogenic activity of lung cancer cells but not normal bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up-regulation of the expression of cyclin-dependent kinase inhibitor p21. Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a proteasomal degradation of E2F1, leading to suppression of E2F1 function in lung cancer but not normal bronchial epithelial cells. Because E2F1 is overexpressed in lung cancer tumor samples, these data indicate that largazole is an E2F1-targeting cell cycle inhibitor, which bears therapeutic potentials for this malignant neoplasm.