2,2',2"-(10-(2-((6-(3-(((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)-5-iodobenzamido)hexyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid | 1411600-41-3

• 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',2"-(10-(2-((6-(3-(((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)-5-iodobenzamido)hexyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid
• 英文别名: 2-[4,7-Bis(carboxymethyl)-10-[2-[6-[[3-(2,5-dioxopyrrolidin-1-yl)oxycarbonyl-5-iodobenzoyl]amino]hexylamino]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
• CAS: 1411600-41-3
• 化学式: C₃₄H₄₈IN₇O₁₂
• 分子量: 873.699
• InChiKey: MTUMYQFTTFCTJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.5
• 重原子数：
  54
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  247
• 氢给体数：
  5
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  5-碘间苯二甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 2,2',2"-(10-(2-((6-(3-(((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)-5-iodobenzamido)hexyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid
  参考文献：
  名称：

  SIB-DOTA: A trifunctional prosthetic group potentially amenable for multi-modal labeling that enhances tumor uptake of internalizing monoclonal antibodies

  摘要：

  A major drawback of internalizing monoclonal antibodies (mAbs) radioiodinated with direct electrophilic approaches is that tumor retention of radioactivity is compromised by the rapid washout of iodo-tyrosine, the primary labeled catabolite for mAbs labeled via this strategy. In our continuing efforts to develop more versatile residualizing labels that could overcome this problem, we have designed SIB-DOTA, a prosthetic labeling template that combines the features of the prototypical, dehalogenation-resistant N-succinimidyl 3-iodobenzoate (SIB) with DOTA, a useful macrocyclic chelator for labeling with radiometals. Herein we describe the synthesis of the unlabeled standard of this prosthetic moiety, its protected tin precursor, and radioiodinated SIB-DOTA. An anti-EGFRvIII-reactive mAb, L8A4 was radiolabeled with [I-131]SIB-DOTA in 27.1 +/- 6.2% (n = 2) conjugation yields and its targeting properties to the same mAb labeled with [I-125]SGMIB both in vitro and in vivo using U87MG.Delta EGFR cells and xenografts were compared. In vitro paired-label internalization assays showed that the intracellular radioactivity from [I-131]SIB-DOTA-L8A4 was 21.4 +/- 0.5% and 26.2 +/- 1.1% of initially bound radioactivity at 16 and 24 h, respectively. In comparison, these values for [I-125]SGMIB-L8A4 were 16.7 +/- 0.5% and 14.9 +/- 1.1%. Similarly, the SIB-DOTA prosthetic group provided better tumor targeting in vivo than SGMIB over 8 d period. These results suggest that SIB-DOTA warrants further evaluation as a residualizing agent for labeling internalizing mAbs including those targeted to EGFRvIII. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.025

文献信息

• Prosthetic Compounds for Labeling Internalizing Biomolecules
  申请人：DUKE UNIVERSITY

  公开号：US20160074541A1

  公开（公告）日：2016-03-17

  Prosthetic compounds are disclosed that are effective for radiolabeling biomolecules with 18F. Representative biomolecules include antibodies (e.g., monoclonal antibodies (mAbs) and nanobodies (sdAbs)), antibody fragments, and peptides that may have an affinity for particular types of cells, such as cancer cells. The prosthetic compounds effectively address the art-recognized difficulties associated with the retention of radioactivity within the targeted cells, due to internalization of the biomolecule, followed by proteolytic degradation. Representative prosthetic compounds include (i) a succinimidyloxycarbonyl moiety, (ii) a radioactive moiety bearing 18F, and (iii) a charged moiety, i.e., a moiety that is charged under the physiological conditions of the internal cell environment.
• US9839704B2
  申请人：——

  公开号：US9839704B2

  公开（公告）日：2017-12-12