IDD‐1040 | 1151990-14-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: IDD‐1040
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-[5-(dithiolan-3-yl)pentanoyloxy]-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 1151990-14-5
• 化学式: C₅₅H₆₃NO₁₅S₂
• 分子量: 1042.23
• InChiKey: BYQZMLDEICKCMX-PQGFSRBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  73
• 可旋转键数：
  21
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  278
• 氢给体数：
  3
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  紫杉醇 、 Thioctic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.25h， 以69%的产率得到IDD‐1040
  参考文献：
  名称：

  A Novel Paclitaxel Conjugate with Higher Efficiency and Lower Toxicity: A New Drug Candidate for Cancer Treatment

  摘要：

  Paclitaxel-lipoate (IDD-1040)是由两个化合物的化学结合形成的共轭物，通过将硫辛酸基团缩合到紫杉醇的C2'位置。使用体内非小细胞肺癌（NSCLC）异种移植小鼠模型，评估了IDD-1040的抗肿瘤活性和潜在药物可用性。在体内实验中，IDD-1040的最大耐受剂量（MTD）为250毫克/千克，而紫杉醇（PTX）的MTD为20毫克/千克。最有趣的是，IDD-1040表现出更高的抗肿瘤活性，其对肿瘤体积（细胞生长）的抑制活性是剂量依赖性的。该抗肿瘤活性在停止IDD-1040治疗后持续两周，而PTX停止治疗后肿瘤复发，证实IDD-1040表现出优越的肿瘤抑制作用。与PTX治疗类似，IDD-1040治疗期间未观察到明显的体重下降，表明其低毒性。随着时间的推移，动物体重的增加是由于所有小鼠实验组中记录的肿瘤重量的增加。结果还表明，IDD-1040治疗可以降低小鼠的死亡率，比PTX更有效。此外，在IDD-1040的体外分布的初步研究中，粒细胞减少症主要集中在注射后1小时的肝脏中，在24小时内大部分药物被肝脏代谢。所有这些结果都表明IDD-1040作为癌症治疗候选药物具有巨大的潜力。

  DOI：

  10.3390/ijms20194965

文献信息

• [EN] THIOLATED PACLITAXELS FOR REACTION WITH GOLD NANOPARTICLES AS DRUG DELIVERY AGENTS<br/>[FR] PACLITAXELS THIOLÉS DESTINÉS À RÉAGIR AVEC DES NANOPARTICULES D'OR, SERVANT D'AGENTS DE DISTRIBUTION DE MÉDICAMENTS
  申请人：VIRGINIA TECH INTELL PROP

  公开号：WO2009062138A1

  公开（公告）日：2009-05-14

  Thioloated taxane derivatives are linked to colloidal metal particles such as gold nanoparticles for use as antitumor agents. The antitumor agents may be targeted to tumors.

  硫代納二烯衍生物与金纳米粒子等胶体金属颗粒相结合，用作抗肿瘤药剂。这些抗肿瘤药剂可以针对肿瘤。
• DERIVATIVES OF TAXOL AND CLOSELY RELATED COMPOUNDS
  申请人：Rayan Anwar

  公开号：US20100298421A1

  公开（公告）日：2010-11-25

  A cytotoxic composition in which two moieties are conjugated covalently. A first moiety is a tax moiety, selected from the group consisting of taxanes, taxane derivatives, and or other closely relative compounds. A second moiety is an acid moiety selected from the group consisting of lipoic acid, acetylcysteine, compounds having an acidic group.

  一种细胞毒性组合物，其中两个部分被共价结合。第一个部分是一种税萜部分，选择自紫杉烷类、紫杉烷衍生物或其他密切相关化合物的群组。第二个部分是一种酸性部分，选择自硫辛酸、乙酰半胱氨酸、具有酸性基团的化合物的群组。
• Precise ratiometric co-loading, co-delivery and intracellular co-release of paclitaxel and curcumin by aid of their conjugation to the same gold nanorods to exert synergistic effects on MCF-7/ADR cells
  作者：Shaohui Xu、Zhu Jin、Zhipeng Zhang、Wei Huang、Yuanyuan Shen、Zhongmin Wang、Shengrong Guo

  DOI：10.1016/j.jddst.2019.101383

  日期：2019.12

  It is necessary for effective combinational effects that multiple chemotherapeutic agents enter and act on the same tumor cells simultaneously at a suitable ratio. Due to their individual physicochemical or biopharmaceutical properties, they cannot reach the same cells at its predetermined ratio after co-administration. Herein, we report a novel system with precise ratiometric co-loading, co-delivery and intracellular co-release of paclitaxel (PTX) and curcumin (CUR), to investigate their synergistic effects. We prepared the system by conjugating PTX and CUR at different ratios onto the same gold nanorods (GNRs). We demonstrated that PTX and CUR could be precisely ratiometric co-loaded to form dual-drug conjugated biotin-PEG modified GNRs (abbreviated as PTX/ CUR@BPGNRs), which could co-deliver dual drugs into tumor cells with a predetermined ratio and co-release them intracellularly. The PTX/CUR@BPGNRs with the mass ratio of PTX and CUR at 1:1 exhibited the best synergistic effect on multidrug resistant MCF-7/ADR cells while the free PTX and CUR mixture with the mass ratio of at 1:0.75 displayed the strongest synergism. Cytotoxicity studies showed that PTX/CUR@BPGNRs are superior to free drug mixture. Furthermore, PTX/CUR@BPGNRs could remarkably induce apoptosis of MCF-7/ ADR cells under near-infrared irradiation. Moreover, we found that PTX/CUR@BPGNRs significantly inhibited P-glycoprotein (P-gp) expression in MCF-7/ADR cells.
• US8586625B2
  申请人：——

  公开号：US8586625B2

  公开（公告）日：2013-11-19