IRDye800CW NHS ester | 1207667-09-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: IRDye800CW NHS ester
• 英文别名: 2-[(E)-2-[(3E)-3-[(2E)-2-[3,3-dimethyl-5-sulfo-1-(4-sulfobutyl)indol-2-ylidene]ethylidene]-2-(4-sulfophenoxy)cyclohexen-1-yl]ethenyl]-1-[6-(2,5-dioxopyrrolidin-1-yl)oxy-6-oxohexyl]-3,3-dimethylindol-1-ium-5-sulfonate
• CAS: 1207667-09-1
• 化学式: C₅₀H₅₇N₃O₁₇S₄
• 分子量: 1100.28
• InChiKey: QNRYNBVEVXMFPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  74
• 可旋转键数：
  20
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  333
• 氢给体数：
  3
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  IRDye800CW NHS ester 、 (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido)pentanedioic acid 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以60%的产率得到1-[6-[[(5S)-5-carboxy-5-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]pentyl]amino]-6-oxohexyl]-2-[(E)-2-[(3E)-3-[(2E)-2-[3,3-dimethyl-5-sulfo-1-(4-sulfobutyl)indol-2-ylidene]ethylidene]-2-(4-sulfophenoxy)cyclohexen-1-yl]ethenyl]-3,3-dimethylindol-1-ium-5-sulfonate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Low Molecular Weight Fluorescent Imaging Agents for the Prostate-Specific Membrane Antigen

  摘要：

  Targeted near-infrared (MR) optical imaging can be used in vivo to detect specific tissues, including malignant cells. A series of NIR fluorescent ligands targeting the prostate-specific membrane antigen (PSMA) was synthesized and each compound was tested for its ability to image PSMA+ tissues in experimental models of prostate cancer. The agents were prepared by conjugating commercially available active esters of NIR dyes, including IRDye800CW, IRDye800RS, Cy5.5, Cy7, or a derivative of indocyanine green (ICG) to the terminal amine group of (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido)pentanedioic acid 1, (14S,18S)-1-amino-8,16-dioxo-3,6-dioxa-9,15,17-triazaicosane-14,18,20-tricarboxylic acid 2 and (3S,7S)-26-amino-5,13,20-trioxo-4,6,12,21-tetraaza-hexacosane-1,3,7,22-tetracarboxylic acid 3. The K-i values for the dye-inhibitor conjugates ranged from 1 to 700 pM. All compounds proved capable of imaging PSMA+ tumors selectively to varying degrees depending on the choice of fluorophore and linker. The highest tumor uptake was observed with IRDye800CW employing a poly(ethylene glycol) or lysine suberate linker, as in 800CW-2 and 800CW-3, while the highest tumor to nontarget tissue ratios were obtained for Cy7 with these same linkers, as in Cy7-2 and Cy7-3. Compounds 2 and 3 provide useful scaffolds for targeting of PSMA+ tissues in vivo and should be useful for preparing NIR dye conjugates designed specifically for clinical intraoperative optical imaging devices.

  DOI：

  10.1021/bc3003919

文献信息

• Development of a Novel Histone Deacetylase-Targeted Near-Infrared Probe for Hepatocellular Carcinoma Imaging and Fluorescence Image-Guided Surgery
  作者：Chu Tang、Yang Du、Qian Liang、Zhen Cheng、Jie Tian

  DOI：10.1007/s11307-019-01389-4

  日期：2020.6

  for HCC detection and fluorescence image-guided resection. ResultsIn in vitro imaging, SAHA was labelled with fluorescein isothiocyanate (FITC) to evaluate targeting property, and the imaging results demonstrated that FITC-SAHA was specific uptake by HCC Bel-7402 cells. In in vivo imaging, near infrared fluorescence dye IRDye800CW-labelled SAHA (NIR probe IRDye800CW-SAHA) showed rapid tumor accumulation

  目的肝细胞癌（HCC）是世界范围内常见的癌症，完全手术切除病变组织是治愈癌症的可靠策略。荧光图像引导手术是外科医生识别和去除恶性病变的有前途的工具。虽然非靶向荧光染料已用于 HCC 诊断和切除，但特异性不足和炎症组织的假阳性摄取导致高复发率或健康肝组织的过度切除。为了规避这些问题，我们专注于开发新的肿瘤特异性靶向探针，以在手术过程中选择性地照亮癌症区域。鉴于 HCC 和许多其他癌症中组蛋白去乙酰化酶 (HDAC) 的过度表达，HDAC 靶向成像已成为一种很有前途的肿瘤检测工具。 程序最近，在 HCC 患者的肿瘤样本中观察到 HDAC，特别是 HDAC6 的高表达，并且一些 HDAC 抑制剂，包括 FDA 批准的辛二酰苯胺异羟肟酸 (SAHA)，对 HCC 显示出有效的抗肿瘤作用。相应地，在本研究中，我们利用具有高 HDAC 结合亲和力的小分子 SAHA 作为 HCC 特异性靶向配体开发 HDAC
• A selenium-containing selective histone deacetylase 6 inhibitor for targeted <i>in vivo</i> breast tumor imaging and therapy
  作者：Chu Tang、Yang Du、Qian Liang、Zhen Cheng、Jie Tian

  DOI：10.1039/c9tb00383e

  日期：——

  management of breast cancer, especially for triple-negative breast cancer (TNBC). However, current imaging methods and treatment strategies are ineffective because of the lack of efficient biomarkers and molecular targets. Thus, identifying novel biomarkers and their corresponding ligands is critical for controlling breast cancer. Histone deacetylase 6 (HDAC6) has emerged as a valid target for cancer therapy

  早期发现和有效治疗对于乳癌尤其是三阴性乳腺癌（TNBC）的治疗至关重要。然而，由于缺乏有效的生物标志物和分子靶标，当前的成像方法和治疗策略是无效的。因此，鉴定新的生物标志物及其相应的配体对于控制乳腺癌是至关重要的。组蛋白脱乙酰基酶6（HDAC6）由于具有选择性的肿瘤抑制作用和与pan-HDAC-和HDAC1-3异构体选择性抑制剂相比较少的副作用，已成为癌症治疗的有效靶点。在这里，通过利用硒氰化物部分代替常规的异羟肟酸核心开发了HDAC6选择性抑制剂SelSA，后者相对于HDAC1和HDAC8对HDAC6表现出112倍和128倍的选择性结合亲和力。体外研究表明，ERTC（+）MCF-7和TNBC MDA-MB-231细胞都主要摄取FITC-SelSA，主要存在细胞质定位。SelSA重新激活ERα表达，并使TNBC细胞对拮抗剂他莫昔芬敏感，并在体外和体内对MCF-7和MDA-MB-231细胞均
• (<i>S</i>)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging
  作者：Xiaojiang Duan、Futao Liu、Hongmok Kwon、Youngjoo Byun、Il Minn、Xuekang Cai、Jingming Zhang、Martin G. Pomper、Zhi Yang、Zhen Xi、Xing Yang

  DOI：10.1021/acs.jmedchem.9b02031

  日期：2020.4.9

  prostate-specific membrane antigen (PSMA), 16 ligands (L1–L16) with structural modifications in S1′ binding pocket were synthesized and evaluated for PSMA inhibition. (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acids proved to be potent PSMA ligands with Ki values ranging from 0.08 nM to 8.98 nM, which are in the range of or are higher in potency compared to previously published urea-based

  为了寻求针对前列腺特异性膜抗原（PSMA）的新型药物，合成了16种在S1'结合口袋中具有结构修饰的配体（L1 - L16），并评估了其对PSMA的抑制作用。（S）-3-（羧甲酰胺基）-2-（3-（羧甲基）脲基）丙酸已被证明是有效的PSMA配体，其K i值在0.08 nM至8.98 nM范围内，或更高。与以前发布的基于尿素的配体相比，其效价更高。进行计算对接以研究发现的两个最有效配体的结合模式。FITC偶联的L14可以选择性地将PSMA + LNCaP细胞染色到PSMA之上–PC3细胞。IRDye800CW缀合的L16可以有效地在前列腺癌的小鼠异种移植模型中对肿瘤成像。
• [EN] SYNTHESIS AND APPLICATION OF NOVEL IMAGING AGENTS CONJUGATED TO DPA 713 ANALOGS FOR IMAGING INFLAMMATION<br/>[FR] SYNTHÈSE ET APPLICATION DE NOUVEAUX AGENTS D'IMAGERIE CONJUGUÉS À DES ANALOGUES DU DPA 713 POUR L'EXAMEN PAR IMAGERIE DE L'INFLAMMATION
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2013138612A1

  公开（公告）日：2013-09-19

  The present invention provides analog compounds of DPA-713 which specifically bind the translocator protein (TSPO), which is upregulated in activated leukocytes, some malignant tumors and tissues involved in steroid biogenesis. These compounds are linked via a linking moiety to a variety of imaging agents, including, for example, near infra-red dyes. The compounds of the present invention are useful for both pre-clinical near-IR fluorescence imaging (NIRF) and use in optically-guided interventions including NIRF endoscopy. Methods of use in diagnosis and treatment of TSPO related disease are also provided.

  本发明提供了DPA-713的类似化合物，这些化合物特异性地结合转运蛋白（TSPO），该蛋白在活化白细胞、某些恶性肿瘤和类固醇生物合成涉及的组织中上调。这些化合物通过连接基团与各种成像剂（例如近红外染料）结合。本发明的化合物对于预临床近红外荧光成像（NIRF）和用于光学引导干预（包括NIRF内窥镜）都有用。还提供了在TSPO相关疾病的诊断和治疗中使用的方法。
• Synthesis of Conjugatable Bisphosphonates for Molecular Imaging of Large Animals
  作者：Kumar R. Bhushan、Eiichi Tanaka、John V. Frangioni

  DOI：10.1002/anie.200701216

  日期：2007.10.22