MA-GFLG-docetaxel | 1221403-99-1

• 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: MA-GFLG-docetaxel
• 英文别名: 2'-O-methacryloylglycylphenylalanylleucylglycyl-docetaxel；N-methacryloylglycylphenylalanylleucylglycyldocetaxel
• CAS: 1221403-99-1
• 化学式: C₆₆H₈₃N₅O₁₉
• 分子量: 1250.41
• InChiKey: AYXCBIOEHPTHLZ-TWTWAENWSA-N

物化性质

• 沸点：
  1284.0±65.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  90.0
• 可旋转键数：
  22.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  346.92
• 氢给体数：
  8.0
• 氢受体数：
  19.0

反应信息

• 作为产物：
  描述：

  MA-GFLG-OH 、 多西他赛 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 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以64%的产率得到MA-GFLG-docetaxel
  参考文献：
  名称：

  间隔长度影响靶向多西他赛偶联物在表达前列腺特异性膜抗原的前列腺癌中的功效。

  摘要：

  靶向递送和控释相结合是一种强大的癌症治疗技术。在本文中，我们描述了靶向和非靶向N的设计、合成、结构验证和生物学特性。-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物-多西紫杉醇缀合物。多西紫杉醇 (DTX) 通过四肽间隔基 (-GFLG-) 与 HPMA 共聚物缀合。3-(1,3-二羧丙基)-脲基]戊二酸(DUPA) 用作靶向部分以主动递送DTX 以治疗表达前列腺特异性膜抗原(PSMA) 的前列腺癌。制备了短间隔和长间隔 DUPA 单体，并通过可逆加成-断裂链转移 (RAFT) 共聚反应制备了四种 HPMA 共聚物 - DTX 共轭物（非靶向，两种靶向不同分子量的短间隔基和靶向长间隔基）。在 C4-2 细胞系上确认 PSMA 表达后，DTX 偶联物在体外针对C4-2肿瘤细胞测试了细胞毒性，并在携带sc人前列腺腺癌C4-2异种移植物的裸鼠中评估了它们的抗癌功效。该体内结果表明，靶向部分和HPM

  DOI：

  10.3109/1061186x.2013.833207

文献信息

• RADIATION ENHANCED MACROMOLECULAR DELIVERY OF THERAPEUTIC AGENTS FOR CHEMOTHERAPY
  申请人：UNIVERSITY OF UTAH RESEARCH FOUNDATION

  公开号：US20160166693A1

  公开（公告）日：2016-06-16

  Described herein are anti-cancer compounds composed of a macromolecule comprising (1) at least one anti-cancer agent directly or indirectly bonded to the macromolecule and (2) at least one high Z element directly or indirectly bonded to the macromolecule that is capable of producing Auger electrons upon exposure to X-ray energy. When the compounds are exposed to low energy X-ray (e.g., kilo electron volts KeV) Auger electrons are produced by the high Z elements present in the compound. Because lower energy is required when compared to typical radiotherapy, which uses therapeutic X-ray energy in the million electron volt range (MeV), the subject experiences lower collateral damage when compared to radiation therapy. Additionally, the presence of the anti-cancer agent provides a second mechanism for killing cancer cells. Methods for making and using the anti-cancer compounds are also described herein.

  本文描述了一种抗癌化合物，由包括（1）至少一种直接或间接与大分子结合的抗癌药物和（2）至少一种直接或间接与大分子结合的高Z元素组成，该高Z元素在暴露于X射线能量时能够产生奥古尔电子。当这些化合物暴露于低能量X射线（例如，千电子伏特KeV）时，化合物中存在的高Z元素会产生奥古尔电子。与使用百万电子伏特范围内的治疗性X射线能量（MeV）的典型放射疗法相比，所需的能量更低，因此受试者在与放射疗法相比时经历较低的附带损伤。此外，抗癌药物的存在提供了杀死癌细胞的第二机制。本文还描述了制备和使用抗癌化合物的方法。
• Polymeric drug delivery conjugates and methods of making and using thereof
  申请人：Pan Huaizhong

  公开号：US09289510B2

  公开（公告）日：2016-03-22

  Described herein are biodegradable drug delivery conjugates for effectively delivering bioactive agents to a subject. The drug delivery conjugates comprise a water-soluble high molecular weight linear biodegradable polymer backbone comprising a plurality of linear water-soluble polymeric segments connected to one another by a first (main-chain) cleavable linker, wherein a bioactive agent is covalently bonded to at least one water-soluble polymeric segment, at least one cleavable linker, or a combination thereof. The conjugates possess numerous advantages over prior art delivery conjugates. Also described herein are methods for making and using the conjugates.

  本文描述了一种可降解的药物传递共轭物，用于有效地将生物活性剂传递给受试者。药物传递共轭物包括水溶性高分子量线性可降解聚合物骨架，该骨架包括通过第一（主链）可切割连接子连接在一起的多个线性水溶性聚合物段，其中生物活性剂与至少一个水溶性聚合物段、至少一个可切割连接子或二者的组合共价结合。这些共轭物相对于先前技术的传递共轭物具有许多优点。本文还描述了制备和使用这些共轭物的方法。
• Comparison of Active and Passive Targeting of Docetaxel for Prostate Cancer Therapy by HPMA Copolymer–RGDfK Conjugates
  作者：Abhijit Ray、Nate Larson、Daniel B. Pike、Michele Grüner、Sachin Naik、Hillevi Bauer、Alexander Malugin、Khaled Greish、Hamidreza Ghandehari

  DOI：10.1021/mp100402n

  日期：2011.8.1

  N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-docetaxel-RGDfk conjugate was synthesized, characterized, and evaluated in vitro and in vivo in comparison with untargeted low and high molecular weight HPMA copolymer docetaxel conjugates. The targeted conjugate was designed to have a hydrodynamic diameter below renal threshold to allow elimination post treatment. All conjugates demonstrated the ability to inhibit the growth of DU14S and PC3 human prostate cancer cells and the HUVEC at low nanomolar concentrations. The targeted conjugate showed active binding to alpha(v)beta(3) integrins in both HUVEC and DU145 cells, whereas the untargeted conjugate demonstrated no evidence of specific binding. Efficacy at two concentrations (20 mg/kg and 40 mg/kg) was evaluated in nu/nu mice bearing DU145 tumor xenografts treated with a single dose of conjugates and compared with controls. RGDfK targeted and high molecular weight nontargeted conjugates exhibited the highest antitumor efficacy as evaluated by tumor regression. These results demonstrate that alpha(v)beta(3) integrin targeted polymeric conjugates with improved water solubility, reduced toxicity and ease of elimination post treatment in vivo are promising candidates for prostate cancer therapy.