Tyr³-octreotide | 103667-46-5

• 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: Tyr³-octreotide
• 英文别名: D-Phe-c[Cys-Tyr-D-Trp-Lys-Thr-Cys]-Thr(ol)；H-D-Phe-Cys(1)-Tyr-D-Trp-Lys-Thr-Cys(1)-Thr-ol；(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-N-[(2R,3R)-1,3-dihydroxybutan-2-yl]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide
• CAS: 103667-46-5
• 化学式: C₄₉H₆₆N₁₀O₁₁S₂
• 分子量: 1035.26
• InChiKey: LHCIROHUTQLZCZ-BGCOXABYSA-N

物化性质

• 沸点：
  1481.0±65.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  72
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  403
• 氢给体数：
  14
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  Tyr³-octreotide 在 sodium iodide 、 1,3,4,6-四氯-3α,6α-二苯基甘脲 作用下， 以 二甲基亚砜 为溶剂， 生成 Tyr(3)-octreotide I-125
  参考文献：
  名称：

  177Lu 标记的生长抑素-2 受体靶向金属组装体的合成：超分子放射治疗设计中的挑战

  摘要：

  自组装超分子配位复合物（SCC）在癌症治疗的生物医学应用中具有广阔的前景，尽管它们在核医学领域的潜力尚未得到充分开发。因此，在本研究中，外型功能化的阳离子 [Pd 2 L 2 ] 4+金属环（L = 3,5-双（3-乙炔基吡啶）苯基）靶向生长抑素-2 受体 (sst2R)，并具有 DOTA 螯合剂(1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸)为了结合β-和γ-发射体镥-177，通过标准固体配体合成后通过自组装合成-相肽合成（SPPS）。然后通过反相高效液相色谱 (RP-HPLC)、电喷雾电离质谱 (ESI-MS) 以及1 H 和1 H-DOSY NMR（DOSY = 扩散有序光谱）对该金属环进行表征。还优化了用177 Lu 放射性标记金属环的程序。评估了所得的[ nat/177 Lu]Lu-DOTA-金属环，称为[ nat/177 Lu]Luc- Cy ，其稳定性和体外特性。与参考[

  DOI：

  10.1021/acs.inorgchem.3c02090
• 作为产物：
  描述：

  Lys5(Dde)-Tyr3-octreotide 在 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 Tyr³-octreotide
  参考文献：
  名称：

  N-Terminal Sugar Conjugation and C-Terminal Thr-for-Thr(ol) Exchange in Radioiodinated Tyr³-octreotide:  Effect on Cellular Ligand Trafficking in Vitro and Tumor Accumulation in Vivo

  摘要：

  For effective targeting of somatostatin receptor (sst) expressing tumors by radiolabeled octreotide analogues, high ligand uptake into sst-positive cells is mandatory. To optimize it, two modifications have been introduced into [I-125]Tyr(3)-octreotide ([I-125]TOC): C-terminal Thr-for-Thr(ol) exchange (leading to Tyr(3)-octreotate (TOCA)) and N-terminal derivatization with different carbohydrates. Both have significant impact on radioligand uptake into sst(2)-expressing cells in vitro and in vivo. Glucose conjugation via Amadori reaction by itself led to improved tumor uptake of [I-123] Gluc-TOC in vivo, which is based on an enhancement of peptide internalization despite a reduction in receptor affinity. In the case of the doubly modified analogues [I-123]Gluc-TOCA, [I-123]Gluc-S-TOCA, and [I-123] Gal-S-TOCA, a cumulative effect of both structural modifications was observed, leading up to a 5-fold increased uptake of these compounds in sst-expressing tumors compared to [I-125]TOC. Thus, glycosylation with small carbohydrates was found to be a suitable tool to enhance receptor-mediated uptake of radiolabeled octreotide analogues into sst-positive malignancies, leading to tracers with excellent characteristics for in vivo sst-imaging applications.

  DOI：

  10.1021/jm040794i

文献信息

• Reversible Lipidization Prolongs the Pharmacological Effect, Plasma Duration, and Liver Retention of Octreotide
  作者：Liyun Yuan、Jeff Wang、Wei-Chiang Shen

  DOI：10.1007/s11095-004-1189-z

  日期：2005.2

  Octreotide (OCT) was reversibly lipidized to improve the pharmacological effect and to increase the plasma half-life and the liver retention of OCT for greater therapeutic potential in the treatment of liver cancers such as hepatocellular carcinoma. OCT was chemically modified using reversible aqueous lipidization (REAL) technology. REAL-modified OCT (REAL-OCT) was characterized with high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. A single dose of OCT or REAL-OCT or vehicle only was subcutaneously administered to male Sprague-Dawley rats, and the plasma growth hormone (GH) levels were measured after an intravenous injection of 2.5 μg/kg of growth hormone releasing factor (GRF) to assess the ability of REAL-OCT on GH inhibition. Radio-iodinated Tyr3-OCT (TOC) and REAL-TOC were used for pharmacokinetic studies. At 0.1 mg/kg, REAL-OCT inhibited the GRF-induced GH surge in rats for a greater than 24-h period in comparison to the 6-h period for OCT. The distribution and elimination half-life for 125I-REAL-TOC were 1.4 h and 6.6 h, respectively, which were significantly longer than those of 125I-TOC. Sustained high blood concentrations and reduced in vivo degradation were observed for 125I-REAL-TOC. In addition, 125I-REAL-TOC appeared to be targeted to the liver with persistent high liver retention. REAL-OCT has a significantly enhanced pharmacological effect, and this is most likely due to the favorable changes in the pharmacokinetic parameters upon lipidization. The observed liver targeting effect of REAL-TOC suggests that REAL-OCT might be advantageous over OCT in treating liver cancers.

  对奥曲肽 (OCT) 进行了可逆脂化处理，以改善其药理作用，并延长其血浆半衰期和肝脏保留时间，从而提高其在治疗肝癌（如肝细胞癌）方面的治疗潜力。我们利用可逆水性脂化（REAL）技术对 OCT 进行了化学修饰。REAL修饰的OCT（REAL-OCT）采用高效液相色谱法（HPLC）和基质辅助激光解吸电离飞行时间质谱法（MALDI-TOF）进行表征。给雄性 Sprague-Dawley 大鼠皮下注射单剂量的 OCT 或 REAL-OCT 或仅用载体，在静脉注射 2.5 μg/kg 生长激素释放因子（GRF）后测定血浆生长激素（GH）水平，以评估 REAL-OCT 抑制 GH 的能力。放射性碘化Tyr3-OCT（TOC）和REAL-TOC被用于药代动力学研究。在 0.1 毫克/千克的剂量下，REAL-OCT 可抑制 GRF 诱导的大鼠 GH 激增超过 24 小时，而 OCT 只需 6 小时。125I-REAL-TOC的分布半衰期和消除半衰期分别为1.4小时和6.6小时，明显长于125I-TOC。125I-REAL-TOC 的血药浓度持续较高，体内降解减少。此外，125I-REAL-TOC 似乎以肝脏为靶点，具有持续的高肝保留率。REAL-OCT 的药理作用明显增强，这很可能是由于脂化后药代动力学参数发生了有利的变化。所观察到的 REAL-TOC 的肝脏靶向效应表明，在治疗肝癌方面，REAL-OCT 可能比 OCT 更具优势。
• [EN] LIGAND COMPOUNDS COMPRISING A CHELATING GROUP AS A BRIDGING GROUP<br/>[FR] COMPOSÉS LIGANDS COMPRENANT UN GROUPE CHÉLATEUR EN TANT QUE GROUPE PONTANT
  申请人：UNIV MUENCHEN TECH

  公开号：WO2023012282A1

  公开（公告）日：2023-02-09

  Provided is a compound selected from (a) a compound of formula (I) wherein a is 0 or 1; m is 2 or 3; n is 2 or 3; one group selected from R1, R2and R3is a group comprising an effector moiety RB; another group selected from R1, R2and R3is a group comprising a silicon-based fluoride acceptor (SiFA) moiety Rs; and the remaining group selected from R1, R2 and R3 is a group of the formula (R-1) wherein R4is selected from -H, -OH and C1-C3 alkyl; and wherein the dashed line marks a bond which attaches the group to the remainder of the compound; R5is selected from -H, -OH and C1 -C3 alkyl; (b) a salt thereof, and (c) a chelate compound formed from a compound of formula (I) or its salt, and a radioactive or non-radioactive cation. The compounds of the invention are suitable for therapeutic and diagnostic purposes such as radionuclide therapy or nuclear diagnostic imaging.

  提供了一种选自 (a) 式 (I) 的化合物 其中 a 是 0 或 1；m 是 2 或 3；n 是 2 或 3；一个选自 R1、R2 和 R3 的基团是包含效应分子 RB 的基团；另一个选自 R1、R2 和 R3 的基团是包含硅基氟化物受体 (SiFA) 分子 Rs 的基团；其中 R4 选自-H、-OH 和 C1-C3 烷基；虚线表示将该基团连接到化合物其余部分的键；R5 选自-H、-OH 和 C1-C3 烷基；(b) 其盐，以及 (c) 由式 (I) 化合物或其盐与放射性或非放射性阳离子形成的螯合物。本发明的化合物适用于治疗和诊断目的，如放射性核素治疗或核素诊断成像。
• Synthesis of trifunctional somatostatin based derivatives for improved cellular and subcellular uptake
  作者：Mihaela Ginj、Helmut R. Maecke

  DOI：10.1016/j.tetlet.2005.02.117

  日期：2005.4

  It is now well established that the biological effects of Auger-emitting radionuclides are critically dependent on their subcellular location. Therefore, for their use in molecular imaging and targeted radionuclide therapy, attempts should be made to increase the nuclear specificity of the carriers. In the present paper the synthesis of novel trifunctional somatostatin derivatives containing a nuclear localization motif is described. These derivatives of [DOTA(0), Tyr(3)]-octreotide (DOTATOC, DOTA = 1,4,7, 1 O-tetraazacyclododecane-1,4,7.10-tetraacetic acid) were obtained in high yields using Fmoc peptide synthesis in solid and in solution phase. (c) 2005 Elsevier Ltd. All rights reserved.
• Chuang, Pei-Chun; Chang, Shiang-Rong; Wen, Shu-Hwai, Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S303 - S304
  作者：Chuang, Pei-Chun、Chang, Shiang-Rong、Wen, Shu-Hwai、Chen, Shu-Ling、Ting, Gann、Lee, Te-Wei

  DOI：——

  日期：——
• Synthesis and radiolabeling of 111In-core-cross linked polymeric micelle-octreotide for near-infrared fluoroscopy and single photon emission computed tomography imaging
  作者：Ye Hong、Hua Zhu、Ji Hu、Xinfeng Lin、Feng Wang、Chun Li、Zhi Yang

  DOI：10.1016/j.bmcl.2014.03.050

  日期：2014.6

  The objective of this study was the development of a dual-modality imaging device, namely In-111-core-cross-linked polymeric micelle (CCPM)-octreotide, for neuroendocrine tumor detection, using near-infrared fluoroscopy (NIRF) and single photon emission computed tomography (SPECT). The tumor targeting ability of the In-111-labeled CCPM-octreotide was evaluated in a tumor mouse model. SPECT/CT, NIRF and gamma imaging results showed high tumor uptake of In-111-labeled CCPM-octreotide. In contrast, there was a much lower signal in the same mouse model injected with In-111-labeled CCPM. The high accumulation of In-111-labeled CCPM-octreotide in U87 tumor was reduced after co-injection with an excess amount of CCPM-octreotide. These results suggested CCPM-octreotide's potential applications in tumor diagnosis, drug delivery and molecular imaging. (C) 2014 Elsevier Ltd. All rights reserved.