Cyclo(Arg-Ala-Asp-(D-Tyr)-Lys) | 1193347-53-3

• 物质功能分类: 生物 - 蛋白与多肽
• 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: Cyclo(Arg-Ala-Asp-(D-Tyr)-Lys)
• 英文别名: 2-[(2S,5R,8S,11S,14S)-8-(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-14-methyl-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
• CAS: 1193347-53-3
• 化学式: C₂₈H₄₃N₉O₈
• 分子量: 633.705
• InChiKey: FAILKIOFKCFNBU-KJRRRBQDSA-N

物化性质

• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  293
• 氢给体数：
  10
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidin-1-yl 4-((3-(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamido)propyl)amino)-4-oxobutanoate 、 Cyclo(Arg-Ala-Asp-(D-Tyr)-Lys) 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到
  参考文献：
  名称：

  Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy

  摘要：

  两种源于MEK1/2激酶抑制剂PD0325901的新型RGD-MEKI偶联物系列已被开发用于整合素受体介导的癌症治疗。第一系列，烷氧基胺类似物RGD-MEKI偶联物9a-g通过与PD0325901相同的机制在黑色素瘤A375细胞中显示出抗增殖活性。PEGylation使9f在A375测定中的IC50值增加了三倍，而多cRGD肽负载则显著提高了9g在整合素高表达的U87细胞中的受体特异性抗增殖活性。在第二系列中，RGD-PD0325901 13相比烷氧基胺类似物，通过抑制ERK通路活性和癌细胞的DNA复制，显示出显著增强的抗肿瘤特性。此外，13在U87测定中比PD0325901显示出更强的抗增殖活性，且呈剂量依赖性。所有这些数据表明，带有酯键连接的RGD-MEKI偶联物提高了对整合素高表达肿瘤细胞的靶向能力，从而增强了抗癌疗效。

  DOI：

  10.3390/molecules181113957

文献信息

• Cyclopeptides Containing RGD Mimetics As Imaging Markers For Integrins
  申请人：Kolb Hartmuth C.

  公开号：US20100074844A1

  公开（公告）日：2010-03-25

  Radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

  放射性标记的环状多肽、包含放射性标记的环状多肽的药物组合物，以及使用放射性标记的环状多肽的方法。这些多肽可用于影像研究，如正电子发射断层摄影（PET）或单光子发射计算机断层摄影（SPECT）。
• US8133472B2
  申请人：——

  公开号：US8133472B2

  公开（公告）日：2012-03-13
• [EN] CYCLOPEPTIDES CONTAINING RGD MIMETICS AS IMAGING MARKERS FOR INTEGRINS<br/>[FR] CYCLOPEPTIDES CONTENANT DES MIMÉTIQUES RGD SERVANT DE MARQUEURS D'IMAGERIE POUR DES INTÉGRINES
  申请人：SIEMENS MEDICAL SOLUTIONS

  公开号：WO2009134382A2

  公开（公告）日：2009-11-05

  Radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT). The radionuclide label is a positron or gamma emitter, e.g. 18F. The polypeptide core is a backbone cyclic RGD derivative of formula: (I) wherein R1 and R8 are side chains of natural or unnatural amino acids and w is an integer from 1 to 5.
• Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy
  作者：Xiaoxiao Li、Jianjun Hou、Chao Wang、Xinjie Liu、Hongyan He、Ping Xu、Zhenjun Yang、Zili Chen、Yun Wu、Lihe Zhang

  DOI：10.3390/molecules181113957

  日期：——

  Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor—PD0325901—have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog RGD-MEKI conjugates 9a–g showed anti-proliferation activity in melanoma A375 cells by the same mechanism as that of PD0325901. PEGylation increased the IC50 value of 9f three-fold in the A375 assay, and the multi-cRGD peptide cargo significantly improved the receptor specific anti-proliferation activity of 9g in integrin-overexpressing U87 cells. In the second series, RGD-PD0325901 13 exhibited significantly increased antitumor properties compared to the alkoxylamine analogs by both inhibition of the ERK pathway activity and DNA replication of the cancer cells. Furthermore, 13 displayed more potent anti-proliferation activity in the U87 assay than PD0325901 in a dose-dependent manner. All these data demonstrate that RGD-MEKI conjugates with an ester bond linkage enhanced anticancer efficacy with improved targeting capability toward integrin-overexpressing tumor cells.

  两种源于MEK1/2激酶抑制剂PD0325901的新型RGD-MEKI偶联物系列已被开发用于整合素受体介导的癌症治疗。第一系列，烷氧基胺类似物RGD-MEKI偶联物9a-g通过与PD0325901相同的机制在黑色素瘤A375细胞中显示出抗增殖活性。PEGylation使9f在A375测定中的IC50值增加了三倍，而多cRGD肽负载则显著提高了9g在整合素高表达的U87细胞中的受体特异性抗增殖活性。在第二系列中，RGD-PD0325901 13相比烷氧基胺类似物，通过抑制ERK通路活性和癌细胞的DNA复制，显示出显著增强的抗肿瘤特性。此外，13在U87测定中比PD0325901显示出更强的抗增殖活性，且呈剂量依赖性。所有这些数据表明，带有酯键连接的RGD-MEKI偶联物提高了对整合素高表达肿瘤细胞的靶向能力，从而增强了抗癌疗效。