3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)-N-phenylpropanamide | 1450754-39-8

• 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: 3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)-N-phenylpropanamide
• 英文别名: 3-(3-but-3-ynyldiazirin-3-yl)-N-phenylpropanamide
• CAS: 1450754-39-8
• 化学式: C₁₄H₁₅N₃O
• 分子量: 241.293
• InChiKey: ZRUNZZCUEBDVSZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  18.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  53.82
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  3-(3-(but-3-ynyl)-3H-diazirin-3-yl)propanenitrile 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)-N-phenylpropanamide
  参考文献：
  名称：

  极简主义末端含炔烃的二嗪基光交联剂的设计与合成及其在基于细胞和组织的蛋白质组谱分析的激酶抑制剂中的掺入

  摘要：

  少即是多：极简的“可点击”光交联剂（参见方案）与许多小分子激酶抑制剂结合在一起。所得的探针可用于体外（细胞裂解物）和原位（活细胞）蛋白质组分析，以大规模鉴定其潜在的细胞激酶靶标，并显示出比以前的探针更好的结果。

  DOI：

  10.1002/anie.201300683

文献信息

• Evaluation of site-diversified, fully functionalized diazirine probes for chemical proteomic applications
  作者：Yan Tan、Songsen Fu、Tao Yang、Yuxin Xie、Guyi Shen、Jie Yan、Yufen Zhao、Feng Ni

  DOI：10.1039/d2cc03868d

  日期：——

  A series of site-diversified, fully functionalized diazirine probes are constructed based on a scaffold shared by several marketed EGFR-targeted drugs. The integrated analysis of protein targets of the site-diversified probe toolkit not only unveils more complete target space and helps suggest false positive targets, but also reveals dynamic events of multi-domain target-ligand interaction.

  基于几种已上市的 EGFR 靶向药物共享的支架，构建了一系列位点多样化、功能齐全的二氮丙啶探针。位点多样化探针工具包对蛋白质靶点的综合分析不仅揭示了更完整的靶点空间并有助于提示假阳性靶点，而且揭示了多域靶点-配体相互作用的动态事件。
• Pharmacological Targeting of Vacuolar H+-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer
  作者：Yuezhou Wang、Lei Zhang、Yanling Wei、Wei Huang、Li Li、An-an Wu、Anahita Dastur、Patricia Greninger、Walter M. Bray、Chen-Song Zhang、Mengqi Li、Wenhua Lian、Zhiyu Hu、Xiaoyong Wang、Gang Liu、Luming Yao、Jih-Hwa Guh、Lanfen Chen、Hong-Rui Wang、Dawang Zhou、Sheng-Cai Lin、Qingyan Xu、Yuemao Shen、Jianming Zhang、Melissa S. Jurica、Cyril H. Benes、Xianming Deng

  DOI：10.1016/j.chembiol.2020.06.011

  日期：2020.11

  Multidrug resistance (MDR) in cancer remains a major challenge for the success of chemotherapy. Natural products have been a rich source for the discovery of drugs against MDR cancers. Here, we applied high-throughput cytotoxicity screening of an in-house natural product library against MDR SGC7901NCR cells and identified that the cyclodepsipeptide verucopeptin demonstrated notable antitumor potency. Cytological profiling combined with click chemistry-based proteomics revealed that ATP6V1G directly interacted with verucopeptin. ATP6V1G, a subunit of the vacuolar H+-ATPase (v-ATPase) that has not been previously targeted, was essential for SGC7901NCR cell growth. Verucopeptin exhibited strong inhibition of both v-ATPase activity and mTORC1 signaling, leading to substantial pharmacological efficacy against SGC7901/VCR cell proliferation and tumor growth in vivo. Our results demonstrate that targeting v-ATPase via its V1G subunit constitutes a unique approach for modulating v-ATPase and mTORC1 signaling with great potential for the development of therapeutics against MDR cancers.