SN-38

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: SN-38
• 英文别名: 10-O-Methoxymethyl SN-38；(19S)-10,19-diethyl-19-hydroxy-7-(methoxymethoxy)-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
• 化学式: C₂₄H₂₄N₂O₆
• 分子量: 436.464
• InChiKey: HZXMVIQBXGZKEB-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  98.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  SN-38 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (2,5-dioxopyrrolidin-1-yl) 6-[[(19S)-10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl]oxycarbonylamino]hexanoate
  参考文献：
  名称：

  [EN] IRINOTECAN IMMUNOASSAY
  [FR] IMMUNOESSAI D'IRINOTÉCAN

  摘要：

  新型与伊立替康药物活性代谢物有关的共轭物，以及从这种药物活性代谢物衍生的新型免疫原和由这些免疫原产生的单克隆抗体，可用于生物体液中伊立替康药物活性代谢物的定量和监测的免疫测定中。

  公开号：

  WO2011071672A1
• 作为产物：
  描述：

  7-乙基-10-羟基喜树碱 、 氯甲基甲基醚 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以95%的产率得到SN-38
  参考文献：
  名称：

  A multi-stimuli responsive nanoparticulate SN38 prodrug for cancer chemotherapy

  摘要：

  药物输送系统（DDSs）的改良，加入刺激响应元素，可以显著增加抗癌药物的肿瘤特异性输送。

  DOI：

  10.1039/c6tb02262f

文献信息

• Camptothecin intermediates and prodrugs and methods of preparation thereof
  申请人：University of Kentucky Research Foundation

  公开号：US07064202B1

  公开（公告）日：2006-06-20

  The present invention relates to novel intermediates and prodrugs of camptothecin and related analogs.

  本发明涉及紫杉醇及其相关类似物的新型中间体和前药。
• Irinotecan Immunoassay
  申请人：Salamone Salvatore J.

  公开号：US20110136253A1

  公开（公告）日：2011-06-09

  Novel conjugates of the pharmaceutically active metabolite of irinotecan and novel immunogens derived from this pharmaceutically active metabolite and monoclonal antibodies generated by these immunogens which are useful in immunoassays for the quantification and monitoring of the pharmaceutically active metabolite of irinotecan in biological fluids.

  这句话的中文翻译如下： 这些新型化合物是伊立替康药物活性代谢产物的衍生物，并且还包括从这种药物活性代谢产物中衍生的新型免疫原和由这些免疫原产生的单克隆抗体。这些化合物在生物液体中用于免疫测定，以定量和监测伊立替康药物活性代谢产物的含量。
• A Versatile Prodrug Approach for Liposomal Core-Loading of Water-Insoluble Camptothecin Anticancer Drugs
  作者：Xinli Liu、Bert C. Lynn、Junhong Zhang、Lin Song、David Bom、Wu Du、Dennis P. Curran、Thomas G. Burke

  DOI：10.1021/ja0256212

  日期：2002.7.1

  We describe a versatile prodrug strategy for loading the liposomal lumen with water-insoluble camptothecins. The procedure involves conversion of an active camptothecin analogue to a 20-OR omega-aminoalkanoanic ester prodrug in which R = CO[CH(2)](n)()NH(2) and n = 1-3. The basic amino group of the prodrug serves three roles. First, at pH ranges of 3-5, the amine enhances aqueous solubility. Second, it enhances responsiveness to a transmembrane ammonium sulfate gradient across the liposomal bilayer, thereby facilitating active loading of the agent into the liposomal aqueous core. Third, at a physiological pH of 7 or above (the pH to be encountered following drug release at the tumor site), the nucleophilicity of the amine manifests itself and cyclization to the C-21 carbonyl carbon occurs. This cyclization triggers a rapid and convenient nonenzymatic decomposition process that releases active camptothecin. Accordingly, this novel liposomal approach offers a potential system for tumor-targeting prodrugs of many water-insoluble camptothecins, including the highly lipophilic and clinically attractive analogues SN-38, 9-nitrocamptothecin and DB-67. The rate of formation of the active agent at the tumor site can be controlled through the selection of n (the length of the alkyl spacer group).
• Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates
  作者：Yuqin Yao、Lin Yu、Xiaolan Su、Yuxi Wang、Wenting Li、Yangpin Wu、Xiangzheng Cheng、Hang Zhang、Xian Wei、Hao Chen、Rundong Zhang、Lantu Gou、Xiaoxin Chen、Yongmei Xie、Bo Zhang、Yonghui Zhang、Jinliang Yang、Yuquan Wei

  DOI：10.1016/j.jconrel.2015.09.058

  日期：2015.12

  Antibody-drug conjugates (ADCs), combining monoclonal antibody with high cytotoxicity chemotherapeutic drug (warhead), have been successfully applied for clinical cancer therapy. Linker technology to select and design linker connecting warhead with antibody, is critical to the success of therapeutic ADCs. In this study, three kinds of linkers were designed to connect SN-38, the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100-1000 times more potent than CPT-11, with the anti-HER2 antibody trastuzumab to prepare three different ADC conjugates (T-SN38 A, B and C). Meanwhile, we compared the anti-ovarian cancer effect of these three T-SN38 conjugates with trastuzumab in vitro and in vivo. Our in vitro results showed that T-SN38 A, B and C (drug-to-antibody ratio, DAR = 3.7, 3.2, 3.4) were 2 to 3 times as cytotoxic as SN-38, and the IC50 for these three conjugates on SKOV-3 cell line at 72 h were 5.2 +/- 0.3, 4.4 +/- 0.7, and 5.1 +/- 0.4 nM respectively. In our in vivo studies, T-SN38 conjugates had well targeting ability for tumor tissue and all three of them had much higher anti-ovarian cancer potency than trastuzumab. Among of them, T-SN38 B, which coupled SN-38 with trastuzumab by a carbonate bond, has the best anti-ovarian cancer potency. In conclusion, the novel HER2-targeting ADCs T-SN38 have great potential for HER2-positive ovarian cancer. Moreover, the SN-38-Linkers designed in this study can also be used to connect with other antibodies for the therapy of other cancers. (C) 2015 Elsevier B.V. All rights reserved.
• IRINOTECAN IMMUNOASSAY
  申请人：Salamone Salvatore J.

  公开号：US20110165699A1

  公开（公告）日：2011-07-07

  Novel conjugates of the pharmaceutically active metabolite of irinotecan and novel immunogens derived from this pharmaceutically active metabolite and monoclonal antibodies generated by these immunogens which are useful in immunoassays for the quantification and monitoring of the pharmaceutically active metabolite of irinotecan in biological fluids.