cis-Pt(ethylenediamine)nitrate-chloride | 468724-95-0

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机含氧阴离子化合物
• 英文名称: cis-Pt(ethylenediamine)nitrate-chloride
• 英文别名: {PtenClNO3}；cis-[Pt(ethylenediamine)nitratechloride]；cis-[Pt(ethylenediamine)nitrate-chloride]
• CAS: 468724-95-0
• 化学式: C₂H₈ClN₃O₃Pt
• 分子量: 352.637
• InChiKey: IXTFFXIAYXOXGR-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  cis-Pt(ethylenediamine)nitrate-chloride 在 silver nitrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 ethylenediamine platinum(II) nitrate
  参考文献：
  名称：

  [EN] METHOD FOR PREPARING CELL TARGETING CONJUGATES, AND THE COMPLEXES OBTAINED
  [FR] PROCÉDÉ DE PRÉPARATION DE CONJUGUÉS DE CIBLAGE CELLULAIRE, ET LES COMPLEXES OBTENUS

  摘要：

  公开号：

  WO2013103301A3
• 作为产物：
  描述：

  乙二胺氯化铂(II) 在 silver nitrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 cis-Pt(ethylenediamine)nitrate-chloride
  参考文献：
  名称：

  [EN] METHOD FOR PREPARING CELL TARGETING CONJUGATES, AND THE COMPLEXES OBTAINED
  [FR] PROCÉDÉ DE PRÉPARATION DE CONJUGUÉS DE CIBLAGE CELLULAIRE, ET LES COMPLEXES OBTENUS

  摘要：

  公开号：

  WO2013103301A3

文献信息

• Intracellular Delivery of the p38 Mitogen-Activated Protein Kinase Inhibitor SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1<i>H</i>-imidazole] in Renal Tubular Cells: A Novel Strategy to Treat Renal Fibrosis
  作者：Jai Prakash、Maria Sandovici、Vinay Saluja、Marie Lacombe、Roel Q. J. Schaapveld、Martin H. de Borst、Harry van Goor、Robert H. Henning、Johannes H. Proost、Frits Moolenaar、György Këri、Dirk K. F. Meijer、Klaas Poelstra、Robbert J. Kok

  DOI：10.1124/jpet.106.106054

  日期：2006.10

  During renal injury, activation of p38 mitogen-activated protein kinase (MAPK) in proximal tubular cells plays an important role in the inflammatory events that eventually lead to renal fibrosis. We hypothesized that local inhibition of p38 within these cells may be an interesting approach for the treatment of renal fibrosis. To effectuate this, we developed a renal-specific conjugate of the p38 inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1 H -imidazole] and the carrier lysozyme. First, we demonstrated that SB202190 inhibited the expression of albumin-induced proinflammatory (monocyte chemoattractant protein-1) and transforming growth factor (TGF)-β1-induced profibrotic (procollagen-Iα1) genes over 50% in renal tubular cells (normal rat kidney-52E). Next, we conjugated SB202190 via a carbamate linkage to lysozyme. However, this conjugate rapidly released the drug upon incubation in serum. Therefore, we applied a new platinum(II)-based linker approach, the so-called universal linkage system (ULS), which forms a coordinative bond with SB202190. The SB202190-ULS-lysozyme remained stable in serum but released the drug in kidney homogenates. SB202190-ULS-lysozyme accumulated efficiently in renal tubular cells and provided a local drug reservoir during a period of 3 days after a single intravenous injection. Treatment with SB202190-ULS-lysozyme inhibited TGF-β1-induced gene expression for procollagen-Iα1 by 64% in HK-2 cells. Lastly, we evaluated the efficacy of a single dose of the conjugate in the unilateral renal ischemia-reperfusion rat model. A reduction of intrarenal p38 phosphorylation and α-smooth muscle actin protein expression was observed 4 days after the ischemia-reperfusion injury. In conclusion, we have developed a novel strategy for local delivery of the p38 MAPK inhibitor SB202190, which may be of use in the treatment of renal fibrosis.

  在肾损伤过程中，近端小管细胞中p38丝裂原活化蛋白激酶（MAPK）的激活在炎症事件中起着重要作用，这些事件最终导致肾纤维化。我们假设在这些细胞内局部抑制p38可能是一种治疗肾纤维化的有趣方法。为此，我们开发了一种肾脏特异性的p38抑制剂SB202190 [4-(4-氟苯基)-2-(4-羟基苯基)-5-(4-吡啶基)1H -咪唑]与载体溶菌酶的共轭物。首先，我们证明SB202190能够抑制肾小管细胞（正常大鼠肾脏-52E）中由白蛋白诱导的促炎性（单核细胞趋化蛋白-1）和由转化生长因子（TGF）-β1诱导的促纤维化（前胶原-Iα1）基因的表达超过50%。接下来，我们通过碳酸酯链连接将SB202190与溶菌酶共轭。然而，这种共轭物在血清中孵育时迅速释放药物。因此，我们采用了一种新的基于铂(II)的链接器方法，即所谓的通用链接系统（ULS），该系统与SB202190形成配位键。SB202190-ULS-溶菌酶在血清中保持稳定，但在肾脏匀浆中释放药物。SB202190-ULS-溶菌酶有效地在肾小管细胞中积累，并在静脉注射后的3天内提供局部药物储藏。使用SB202190-ULS-溶菌酶处理抑制HK-2细胞中TGF-β1诱导的前胶原-Iα1基因表达64%。最后，我们评估了在单侧肾缺血再灌注大鼠模型中单剂量共轭物的疗效。观察到缺血再灌注损伤后4天，肾内p38磷酸化和α-平滑肌肌动蛋白表达的减少。总之，我们开发了一种新颖的局部递送p38 MAPK抑制剂SB202190的策略，这可能对治疗肾纤维化有用。
• Folate-dactolisib conjugates for targeting tubular cells in polycystic kidneys
  作者：Haili Shi、Wouter N. Leonhard、Niels J. Sijbrandi、Mies J. van Steenbergen、Marcel H.A.M. Fens、Joep B. van de Dikkenberg、Javier Sastre Toraño、Dorien J.M. Peters、Wim E. Hennink、Robbert Jan Kok

  DOI：10.1016/j.jconrel.2018.11.019

  日期：2019.1

  The aim of the present study was to develop folic acid (FA) conjugates which can deliver the kinase inhibitor dactolisib to the kidneys via folate receptor-mediated uptake in tubular epithelial cells. Dactolisib is a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) and is considered an attractive agent for treatment of polycystic kidney disease. The ethylenediamine

  本研究的目的是开发可通过叶酸受体介导的肾小管上皮细胞摄取将激酶抑制剂dactolisib输送至肾脏的叶酸（FA）缀合物。Dactolisib是磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶标（mTOR）的双重抑制剂，被认为是治疗多囊肾疾病的诱人药物。乙二胺铂（II）接头，在本文中称为Lx，用于通过配位化学将dactolisib偶联至含硫醇的FA-间隔物加合物以产生FA-Lx-dactolisib缀合物。染料赖氨酸胺通过类似的接头化学偶联至叶酸，以产生荧光FA-Lx-赖氨酸胺缀合物。三种不同的间隔基（PEG 5 -Cys，PEG 27-Cys或Asp-Arg-Asp-Asp-Cys肽间隔基）用于比较间隔基中的亲水性和带电基团对与靶细胞相互作用和最终缀合物的体内器官分布的影响。最终产品的纯度和身份分别通过UPLC和LC-MS分析确认。FA-Lx-dactolisib结合物在血清和培养基中稳
• Method of conjugating therapeutic compounds to cell targeting moieties via metal complexes
  申请人：Kreatech Biotechnology B.V.

  公开号：EP1745802A1

  公开（公告）日：2007-01-24

  The present invention relates to a cell-targeting complex comprising a targeting moiety and a deliverable compound, wherein said targeting moiety and said deliverable compound are joined by means of a (transition) metal ion complex having at least a first reactive moiety for forming a coordination bond with a reactive site of said targeting moiety and having at least a second reactive moiety for forming a coordination bond with a reactive site of said deliverable compound, and wherein said deliverable compound is a therapeutic compound.

  本发明涉及一种细胞靶向复合物，包括一个靶向基团和一个可传递的化合物，其中所述靶向基团和所述可传递的化合物通过至少具有第一反应基团以形成与所述靶向基团的反应位点形成配位键的(过渡)金属离子复合物连接，并且具有至少具有第二反应基团以形成与所述可传递的化合物的反应位点形成配位键的(过渡)金属离子复合物，其中所述可传递的化合物是一种治疗性化合物。
• Folate decorated polymeric micelles for targeted delivery of the kinase inhibitor dactolisib to cancer cells
  作者：Haili Shi、Mies J. van Steenbergen、Bo Lou、Yanna Liu、Wim E. Hennink、Robbert J. Kok

  DOI：10.1016/j.ijpharm.2020.119305

  日期：2020.5

  micelles which can target folate receptor over-expressing tumor cells. Fluorescently labeled polymeric micelles were prepared using a lissamine-platinum complex linked in a similar manner as dactolisib. Dactolisib polymeric micelles showed good colloidal stability in water and released the coupled drug in buffers containing chloride or glutathione. Folate decorated micelles were avidly internalized by

  聚合胶束临床翻译的主要挑战之一是在系统性给药后将药物保留在纳米载体系统中。药物的核心交联和与胶束骨架的偶联是克服这些问题的常用策略。在本研究中，制备了聚合物微团，用于肿瘤细胞靶向激酶抑制剂dactolisib，后者抑制雷帕霉素（mTOR）激酶和磷脂酰肌醇3-激酶（PI3K）的哺乳动物靶标。我们采用了基于铂（II）的接头化学，以将dactolisib偶联至聚（乙二醇）-b-聚（丙烯酸）（PEG-b-PAA）聚合物胶束的核心。形成的actosolisib-PEG-PAA单体是两亲性的，并在水性环境中自组装成核-壳聚合胶束。将叶酸缀合到胶束的表面上，以产生可靶向叶酸受体过度表达的肿瘤细胞的叶酸修饰的聚合物胶束。荧光标记的聚合物胶束是通过使用与达索利斯（Dactolisib）相似的方式连接的赖氨胺-铂络合物制备的。Dactolisib聚合物胶束在水中显示出良好的胶体稳定性，并在含有氯化物或谷胱甘肽