阿霉素 | 1361644-26-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 中文名称: 阿霉素
• 英文名称: doxorubicin (6-maleimidocaproyl)hydrazone
• 英文别名: aldoxorubicin；INNO-206；N-[(E)-[1-[(2S,4S)-4-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-hydroxyethylidene]amino]-6-(2,5-dioxopyrrol-1-yl)hexanamide
• CAS: 1361644-26-9
• 化学式: C₃₇H₄₂N₄O₁₃
• 分子量: 750.759
• InChiKey: OBMJQRLIQQTJLR-USGQOSEYSA-N

物化性质

• 密度：
  1.60±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：75 mg/mL（99.90 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  54
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  268
• 氢给体数：
  7
• 氢受体数：
  15

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性 Aldoxorubicin (INNO-206) 是多柔比星（DNA 拓扑异构酶 II 抑制剂）的白蛋白结合前药，在酸性条件下从白蛋白中释放。该药物在多种癌细胞系和小鼠肿瘤模型中表现出有效的抗肿瘤活性。

靶点 | Topoisomerase II | Daunorubicins/Doxorubicins |

体外研究 Aldoxorubicin (INNO-206)（浓度范围：0.27至2.16 μM）能够依赖于pH值抑制血管形成并减少多发性骨髓瘤细胞的生长。

体内研究 在体内实验中，Aldoxorubicin (INNO-206)（剂量为10.8 mg/kg，静脉注射）显示出显著减小肿瘤体积和降低IgG水平的效果，在携带LAGκ-1A肿瘤的小鼠中有90%的存活率直至研究结束。该药物在最高达260 mg/mL多柔比星等效剂量下表现出良好的安全性，并能诱导乳腺癌、小细胞肺癌及软组织肉瘤中的肿瘤消退。此外，与多柔比星相比，在肾细胞癌和乳腺癌异种移植模型中，Aldoxorubicin (INNO-206) 表现出更优异的活性。

反应信息

• 作为反应物：
  描述：

  (2-((3-mercaptopropyl)thio)ethane-1,1-diyl)diphosphonic acid 、 阿霉素 在 碳酸氢铵 作用下， 以 水 、 叔丁醇 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  阿霉素新型双膦酸盐前药的开发，用于靶向依赖pH或通过组织蛋白酶B裂解的骨转移：合成，裂解性质和对羟基磷灰石以及骨基质的结合性质

  摘要：

  骨转移是癌症患者发病的常见原因。目前的姑息治疗选择是化学疗法，激素治疗和双膦酸盐的给药。双膦酸盐与骨转移的磷灰石结构之间的亲和力很强。因此，我们设计了两种低分子量和水溶性的前药，它们结合了双膦酸酯基团作为骨靶向配体，阿霉素作为抗癌剂以及酸敏感性键（1）或组织蛋白酶B可裂解键（3）。），以确保在作用部位有效释放阿霉素。两种前药的裂解研究均显示阿霉素可快速释放，但在人血浆中可在数小时内保持足够的稳定性。有效结合前药1并用羟基磷灰石和天然骨证明了3种。在裸鼠的定向毒性研究中，MTD为1是传统阿霉素的3倍，而3则显示出与阿霉素基本相同的MTD。

  DOI：

  10.1021/jm300493m
• 作为产物：
  描述：

  阿霉素 、 6-马来酰亚胺己酸肼 在 三氟乙酸 作用下， 以 甲醇 为溶剂， 生成 阿霉素
  参考文献：
  名称：

  BR96 conjugates of highly potent anthracyclines

  摘要：

  The 6-maleimidocaproylhydrazone derivatives of highly potent antitumor agents 5-Diacetoxypentyidoxorubicin and Morpholinodoxorubicin were synthesized and conjugated to monoclonal antibody BR96 and control IgG. Immunoconjugate molar ratios were generally 7.5-8.5, and dimer aggregate levels were low. The linkers released parent drug at lysosomal pH 5, while they remained stable at neutral pH. BR96 conjugates were highly potent and antigen specific in vitro. The BR96-DAPDOX conjugate demonstrated an IC50 of 0.03 mum, and was at least 300-fold more potent than a non-binding IgG-DAPDOX control conjugate. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00375-5

文献信息

• Combinations of albumin-based drug delivery systems
  申请人：KTB Tumorforschungsgesellschaft mbH

  公开号：EP2630971A1

  公开（公告）日：2013-08-28

  The present invention relates to a composition comprising at least two different albumin-based drug delivery systems, as well as to a pharmaceutical composition comprising said composition.

  本发明涉及一种由至少两种不同的白蛋白给药系统组成的组合物，以及一种由上述组合物组成的药物组合物。
• Anthracycline formulations
  申请人：CYTRX CORPORATION

  公开号：US10328093B2

  公开（公告）日：2019-06-25

  The invention relates to reconstituted formulations comprising an anthracycline compound, ethanol, and water. The invention also relates to injectable compositions comprising the reconstituted formulation and Lactated Ringer's solution. Additionally, the invention relates to methods of using the formulations and compositions.

  本发明涉及由蒽环类化合物、乙醇和水组成的重组制剂。本发明还涉及由重组制剂和乳酸林格氏液组成的注射组合物。此外，本发明还涉及使用这些制剂和组合物的方法。
• Devices and methods for determining and/or isolating cells such as circulating cancer or fetal cells
  申请人：Analiza, Inc.

  公开号：US10928405B2

  公开（公告）日：2021-02-23

  Some embodiments of the present invention generally relate to devices and methods for determining and/or isolating cells. For example, one aspect is generally directed to methods and devices for detecting, identifying, counting, and/or potentially sorting cells of interest in blood or other biological sample. In some embodiments, blood samples (or other biological fluids) may be treated with signaling entities, such as pH-sensitive entities, that change color or otherwise produce a signal in suitable internal environments. For example, certain cells, such as cancer or fetal cells, may have differences in intracellular pH compared to other cells, which can be detected using pH-sensitive entities. In certain embodiments, the cells may be sorted based on such signaling entities; for example, illumination of cells in a suitable machine for sorting cells (e.g., using fluorescent light) may allow determination of the cells, which may also be recovered or isolated for further manipulation in some cases.

  本发明的一些实施方案一般涉及用于确定和/或分离细胞的装置和方法。例如，一个方面一般涉及用于检测、识别、计数和/或可能分选血液或其他生物样本中相关细胞的方法和装置。在某些实施方案中，血液样本（或其他生物液体）可以用信号实体（如 pH 敏感实体）处理，这些实体会变色或在合适的内部环境中产生信号。例如，某些细胞（如癌细胞或胎儿细胞）与其他细胞相比，细胞内 pH 值可能存在差异，可使用 pH 值敏感实体进行检测。在某些实施方案中，可根据此类信号实体对细胞进行分选；例如，在用于分选细胞的合适机器中对细胞进行照射（如使用荧光灯），可对细胞进行测定，在某些情况下，还可对细胞进行回收或分离，以便进一步操作。
• COMBINATIONS OF ALBUMIN-BASED DRUG DELIVERY SYSTEMS
  申请人：KTB TUMORFORSCHUNGSGESELLSCHAFT MBH

  公开号：US20150023912A1

  公开（公告）日：2015-01-22

  The present invention relates to a composition comprising at least two different albumin-based drug delivery systems, as well as to a pharmaceutical composition comprising said composition.
• DEVICES AND METHODS FOR DETERMINING AND/OR ISOLATING CELLS SUCH AS CIRCULATING CANCER OR FETAL CELLS
  申请人：Analiza, Inc.

  公开号：US20150160246A1

  公开（公告）日：2015-06-11

  Some embodiments of the present invention generally relate to devices and methods for determining and/or isolating cells. For example, one aspect is generally directed to methods and devices for detecting, identifying, counting, and/or potentially sorting cells of interest in blood or other biological sample. In some embodiments, blood samples (or other biological fluids) may be treated with signaling entities, such as pH-sensitive entities, that change color or otherwise produce a signal in suitable internal environments. For example, certain cells, such as cancer or fetal cells, may have differences in intracellular pH compared to other cells, which can be detected using pH-sensitive entities. In certain embodiments, the cells may be sorted based on such signaling entities; for example, illumination of cells in a suitable machine for sorting cells (e.g., using fluorescent light) may allow determination of the cells, which may also be recovered or isolated for further manipulation in some cases.