(R)-((S)-1-((2S,3S)-3-hexyl-4-oxooxetan-2-yl)tridecan-2-yl)-4-methyl-2-propiolamidopentanoate | 1204939-00-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-((S)-1-((2S,3S)-3-hexyl-4-oxooxetan-2-yl)tridecan-2-yl)-4-methyl-2-propiolamidopentanoate
• 英文别名: [(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-4-methyl-2-(prop-2-ynoylamino)pentanoate
• CAS: 1204939-00-3
• 化学式: C₃₁H₅₃NO₅
• 分子量: 519.766
• InChiKey: RMIVYOIVYBTQRF-LJWNLINESA-N

物化性质

• 密度：
  0.991±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  37
• 可旋转键数：
  23
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  (3S,4S)-3-己基-4-[(2R)-2-羟基十三烷基]-2-氧杂环丁酮	(3S,4S)-3-hexyl-4-[(R)-2-hydroxytridecyl]-2-oxetanone	104872-06-2	C22H42O3	354.574

反应信息

• 作为产物：
  描述：

  (S)-4-methyl-2-propiolamidopentanoic acid 、 (3S,4S)-3-己基-4-[(2R)-2-羟基十三烷基]-2-氧杂环丁酮 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 以52%的产率得到(R)-((S)-1-((2S,3S)-3-hexyl-4-oxooxetan-2-yl)tridecan-2-yl)-4-methyl-2-propiolamidopentanoate
  参考文献：
  名称：

  Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities

  摘要：

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.

  DOI：

  10.1021/ja907716f

文献信息

• Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities
  作者：Peng-Yu Yang、Kai Liu、Mun Hong Ngai、Martin J. Lear、Markus R. Wenk、Shao Q. Yao

  DOI：10.1021/ja907716f

  日期：2010.1.20

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.