2-({2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl}({2-[bis(carboxy methyl)amino]ethyl})amino)acetic acid | 121806-83-5

• 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: 2-({2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl}({2-[bis(carboxy methyl)amino]ethyl})amino)acetic acid
• 英文别名: 1-(4-isothiocyanatobenzyl)-diethylenetriamine-N,N,N',N'',N''-pentaacetic acid；2-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid；p-SCN-Bn-DPTA；p-SCN-Bn-DTPA；N-{2-[bis(carboxymethyl)amino]ethyl}-N'-{2-[bis(carboxymethyl)amino]-2-(p-isothiocyanatobenzyl)-ethyl}-glycine；2-(p-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid；p-SCN-Benzyl-dtpa；2-[2-[bis(carboxymethyl)amino]ethyl-[2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl]amino]acetic acid
• CAS: 121806-83-5
• 化学式: C₂₂H₂₈N₄O₁₀S
• 分子量: 540.551
• InChiKey: VAOYPHGXHKUTHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  37
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  241
• 氢给体数：
  5
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  N-生物素-3,6-二氧杂辛烷-1,8-二胺 、 2-({2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl}({2-[bis(carboxy methyl)amino]ethyl})amino)acetic acid 在 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2,2'-((2-((2-(bis(carboxymethyl)amino)-3-(4-(3-(2-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)ethoxy)ethoxy)ethyl)thioureido)phenyl)propyl)(carboxymethyl)amino)ethyl)azanediyl)diacetic acid
  参考文献：
  名称：

  Intracellular Routing in Breast Cancer Cells of Streptavidin-Conjugated Trastuzumab Fab Fragments Linked to Biotinylated Doxorubicin-Functionalized Metal Chelating Polymers

  摘要：

  We describe the synthesis of a heterotelechelic metal-chelating polymer (Bi-MCP-Dox), a polyacrylamide with a number average degree of polymerization DPn = 50 (PDI = 1.2), with biotin (Bi) and doxorubicin (Dox) as functional chain ends and diethylenetriaminepentaacetic acid (DTPA) pendant groups as the binding sites for metal ions. We compared its behavior in cell-uptake experiments with a similar polymer (Bi-MCP) without Dox. These MCPs were complexed with trastuzumab Fab (tmFab) fragments covalently linked to streptavidin (SAv) to form tmFab-SAv-Bi-MCP-Dox and tmFab-SAv-Bi-MCP via the strong affinity between Bi and SAv. tmFab targets human epidermal growth factor receptor-2 (HER2), which is overexpressed on certain human breast cancer cells. Surface plasmon resonance (SPR) experiments with the extracellular domain (ECD) of HER2 showed that incorporation of the MCPs in these complexes had no significant effect on the association or dissociation rate with the HER2 ECD and the dissociation constants. The tmFab-complexed MCPs were subsequently labeled with In-111 (an Auger electron emitting radionuclide). Auger electrons can cause lethal DNA double strand breaks (DSBs) but only if they are emitted intracellularly and especially, in close proximity to the nucleus. To evaluate the cellular and nuclear uptake of tmFab-SAv-Bi-MCP-Dox, we incubated HER2+ SK-BR-3 human breast cancer cells with the complexes saturated with stable In3+ and visualized their distribution by confocal fluorescence microscopy, monitoring the fluorescence of Dox. In parallel, we carried out cell fractionation studies on tmFab-SAv-Bi-MCP-Dox and on tmFab-SAv-Bi-MCP labeled with In-111. Both radiolabeled complexes showed cell internalization and nuclear localization. We conclude that metal-chelating polymers with this composition appear to encourage internalization, nuclear uptake, and chromatin (DNA) binding of trastuzumab fragments modified with streptavidin in human breast cancer cells expressing HER2. Further study is needed to understand the impact of polymer charge on cellular uptake and distribution to intracellular compartments.

  DOI：

  10.1021/bm401483a
• 作为产物：
  描述：

  2-({2-[bis(carboxymethyl)amino]-3-(4-nitrophenyl)propyl}({2-[bis(carboxymethyl)amino]ethyl})amino)acetic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 氯仿 、 水 为溶剂， 反应 27.0h， 生成 2-({2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl}({2-[bis(carboxy methyl)amino]ethyl})amino)acetic acid
  参考文献：
  名称：

  SYNTHESIS OF THERAPEUTIC AND DIAGNOSTIC DRUGS CENTERED ON REGIOSELECTIVE AND STEREOSELECTIVE RING OPENING OF AZIRIDINIUM IONS

  摘要：

  通过氮杂环丙烷离子的亲核环开反应，立体选择性和区域选择性合成化合物，用于立体选择性和区域选择性合成治疗和诊断化合物。

  公开号：

  US20130310555A1

文献信息

• RADIOACTIVE COMPOUND FOR DIAGNOSIS OF MALIGNANT MELANOMA AND USE THEREOF
  申请人：INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY

  公开号：US20190336621A1

  公开（公告）日：2019-11-07

  The present invention provides a novel radioactive compound for imaging malignant melanoma and a use thereof as a contrast agent for PET imaging.

  本发明提供了一种用于成像恶性黑色素瘤的新型放射性化合物，以及其作为PET成像对比剂的用途。
• RADIO-PHARMACEUTICAL COMPLEXES
  申请人：Algeta ASA

  公开号：US20150104385A1

  公开（公告）日：2015-04-16

  A tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyl solubilising group and wherein the tissue targeting moiety has binding affinity for the CD22 receptor. Methods of treatment utilising such complexes and methods of formation of such complexes are provided.

  一个组织靶向复合物，包括一个组织靶向基团，一个含有四个HOPO基团的八齿羟基吡啶酮配体和一个α放射性钍放射性核素的离子，其中四个HOPO基团中至少有一个在N位被一个羟基烷基溶解基团取代，并且组织靶向基团具有与CD22受体的结合亲和力。提供了利用这种复合物的治疗方法和这种复合物的形成方法。
• Alpha or beta emitters attached to fragments in radioimmunotherapy
  申请人：Center for Molecular Medicine and Immunology

  公开号：US06667024B1

  公开（公告）日：2003-12-23

  The present invention relates to radioimmunoconjugates useful in targeted radioimmunotherapy and methods of treating a patient using radioimmunoconjugates. The radioimmunoconjugates of the present invention comprise an alpha- or beta-emitting radioisotope and a binding site linked to or on an antigen-binding fragment of an antibody which specifically binds to a tumor-associated antigen. The methods of treating a patient can include administering one or more clearing agents to the patient in conjunction with the radioimmunoconjugate of the present invention, as well as subsequently grafting bone-marrow or autologous stem-cells to the patient.

  本发明涉及用于靶向放射免疫治疗的放射免疫结合物以及使用放射免疫结合物治疗患者的方法。本发明的放射免疫结合物包括α或β放射性同位素和与特异性结合肿瘤相关抗原的抗体的抗原结合片段上或与之连接的结合位点。治疗患者的方法可以包括在与本发明的放射免疫结合物一起向患者施用一个或多个清除剂，以及随后将骨髓或自体干细胞移植给患者。
• COLLAGEN BINDING PEPTIDES
  申请人：Caravan D. Peter

  公开号：US20070293656A1

  公开（公告）日：2007-12-20

  Peptides capable of binding to extracellular matrix proteins, such as collagen, are described, including their use in diagnostic and therapeutic applications.

  描述了能够结合到细胞外基质蛋白（如胶原蛋白）的肽段，包括它们在诊断和治疗应用中的用途。
• ALPHA-EMITTING COMPLEXES
  申请人：Ramdahl Thomas

  公开号：US20130183235A1

  公开（公告）日：2013-07-18

  The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.

  本发明提供了一种组织靶向复合物，包括一个组织靶向基团、一个含有八齿羟基吡啶酮的配体和一个α放射性钍放射性核素的离子。此外，本发明还提供了使用这种复合物的治疗方法、其生产和使用方法，以及包含这种复合物的试剂盒和药物组合物。