H-D-Phe-Cys(1)-Tyr-D-Trp-Lys(Boc)-Thr-Cys(1)-Thr-OH | 177943-94-1

• 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: H-D-Phe-Cys(1)-Tyr-D-Trp-Lys(Boc)-Thr-Cys(1)-Thr-OH
• 英文别名: (2S,3R)-2-[[(4R,7S,10S,13R,16S,19R)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-10-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-hydroxybutanoic acid
• CAS: 177943-94-1
• 化学式: C₅₄H₇₂N₁₀O₁₄S₂
• 分子量: 1149.36
• InChiKey: WJRUKCIGZXDMBE-UOBKEIBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  80
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  432
• 氢给体数：
  14
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  H-D-Phe-Cys(1)-Tyr-D-Trp-Lys(Boc)-Thr-Cys(1)-Thr-OH 、 3-(三苯甲硫基)丙酸-琥珀酰亚胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以54%的产率得到(2S,3R)-3-hydroxy-2-[[(4R,7S,10S,13R,16S,19R)-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-10-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]-6,9,12,15,18-pentaoxo-19-[[(2R)-3-phenyl-2-(3-tritylsulfanylpropanoylamino)propanoyl]amino]-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]butanoic acid
  参考文献：
  名称：

  [EN] TARGETED CONJUGATES AND PARTICLES AND FORMULATIONS THEREOF
  [FR] CONJUGUÉS CIBLÉS, PARTICULES ET PRÉPARATIONS ASSOCIÉES

  摘要：

  公开号：

  WO2016004048A3
• 作为产物：
  描述：

  Fmoc-D-Phe-Cys(1)-Tyr-D-Trp-Lys(Boc)-Thr-Cys(1)-Thr-OH 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 H-D-Phe-Cys(1)-Tyr-D-Trp-Lys(Boc)-Thr-Cys(1)-Thr-OH
  参考文献：
  名称：

  Imaging Somatostatin Positive Tumors with Tyr³-Octreotate/Octreotide Conjugated to Desferrioxamine B Squaramide Radiolabeled with either Zirconium-89 or Gallium-68

  摘要：

  Tyr3-octreotide和Tyr3-octreotate的放射性标记衍生物是肽类激素体生长抑素的合成类似物，可用于神经内分泌肿瘤中体生长抑素受体表达的正电子发射断层扫描（PET）成像。在这项研究中，利用去铁胺 B 的方酰胺酯衍生物（H3DFOSq）将 Tyr3-octreotide 或 Tyr3-octreotate 连接到金属结合配体上，得到 H3DFOSq-TIDE 和 H3DFOSq-TATE。这些新的肽-H3DFOSq共轭物与正电子发射放射性核素镓-68（t1/2 = 68 分钟）或锆-89（t1/2 = 3.3 天）形成稳定的复合物。新复合物在具有 SSTR2 内源性表达的 AR42J 异种移植模型中进行了评估。所有四种制剂都显示出良好的肿瘤摄取率，并生成了高质量的 PET 图像。对于两种放射性核素，与H3DFOSq-TATE形成的复合物表现更好，肿瘤摄取率和保留率均高于与H3DFOSq-TIDE形成的复合物。本文介绍的多功能配体可在室温下用镓-68 或锆-89 进行放射性标记。锆-89的放射性半衰期较长，这使得按照认证标准生产的预合成示踪剂的分发成为可能，并可增加可对神经内分泌肿瘤进行正电子发射计算机断层成像诊断的临床中心的数量。

  DOI：

  10.1021/acs.bioconjchem.1c00109

文献信息

• Targeted conjugates and particles and formulations thereof
  申请人：TARVEDA THERAPEUTICS, INC.

  公开号：US10322191B2

  公开（公告）日：2019-06-18

  Nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker have been designed. Such nanoparticles and microparticles can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

  现已设计出纳米颗粒和微颗粒及其药物制剂，其中含有通过连接体连接到靶向分子（如体生长抑素受体结合分子）的活性剂（如治疗剂、预防剂或诊断剂）的共轭物。这种纳米颗粒和微颗粒可改善活性剂的时间空间递送和/或生物分布。本文提供了共轭物、颗粒及其制剂的制造方法。还提供了向有需要的受试者施用制剂的方法，例如治疗或预防癌症或传染性疾病。
• WO2007/28639
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo
  作者：Brian H. White、Kerry Whalen、Kristina Kriksciukaite、Rossitza Alargova、Tsun Au Yeung、Patrick Bazinet、Adam Brockman、Michelle DuPont、Haley Oller、Charles-Andre Lemelin、Patrick Lim Soo、Benoît Moreau、Samantha Perino、James M. Quinn、Gitanjali Sharma、Rajesh Shinde、Beata Sweryda-Krawiec、Richard Wooster、Mark T. Bilodeau

  DOI：10.1021/acs.jmedchem.8b02036

  日期：2019.3.14

  Somatostatin receptor 2 (SSTR2) is frequently overexpressed on several types of solid tumors, including neuroendocrine tumors and small-cell lung cancer. Peptide agonists of SSTR2 are rapidly internalized upon binding to the receptor and linking a toxic payload to an SSTR2 agonist is a potential method to kill SSTR2-expressing tumor cells. Herein, we describe our efforts towards an efficacious SSTR2-targeting cytotoxic conjugate; examination of different SSTR2-targeting ligands, conjugation sites, and payloads led to the discovery of 22 (PEN-221), a conjugate consisting of microtubule-targeting agent DM1 linked to the C-terminal side chain of Tyr(3)-octreotate. PEN-221 demonstrates in vitro activity which is both potent (IC50 = 10 nM) and receptor-dependent (IC50 shifts 90-fold upon receptor blockade). PEN-221 targets high levels of DM1 to SSTR2-expressing xenograft tumors, which has led to tumor regressions in several SSTR2-expressing xenograft mouse models. The safety and efficacy of PEN-221 is currently under evaluation in human clinical trials.
• TARGETED CONJUGATES AND PARTICLES AND FORMULATIONS THEREOF
  申请人：Tarveda Therapeutics, Inc.

  公开号：US20170095569A1

  公开（公告）日：2017-04-06

  Nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker have been designed. Such nanoparticles and microparticles can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.
• US9750818B2
  申请人：——

  公开号：US9750818B2

  公开（公告）日：2017-09-05