1-azido-3,6,9,12,15-pentaoxaoctadecan-18-oic acid

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 1-azido-3,6,9,12,15-pentaoxaoctadecan-18-oic acid
• 英文别名: azido-peg5-acid；amino-PEG₅-acid；Azido-PEG5-acid；3-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid
• 化学式: C₁₃H₂₅N₃O₇
• 分子量: 335.357
• InChiKey: DPJUPQILWDVIKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  23
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-azido-3,6,9,12,15-pentaoxaoctadecan-18-oic acid 在 盐酸 、 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (9H-fluoren-9-yl)methyl (1-azido-23,23,25,25-tetramethyl-19-oxo-3,6,9,12,15,24-hexaoxa-18-aza-23,25-disilaoctacosan-28-yl)carbamate
  参考文献：
  名称：

  [EN] SILANOL BASED THERAPEUTIC PAYLOADS
  [FR] CHARGES UTILES THÉRAPEUTIQUES À BASE DE SILANOL

  摘要：

  本文部分描述了基于硅醇的治疗载荷，包括硅醇末端、二价间隔基团和能够影响靶细胞或组织的药物基团。

  公开号：

  WO2017214491A1
• 作为产物：
  描述：

  羟丙基淀粉磷酸酯 在 sodium azide 、 sodium 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 1-azido-3,6,9,12,15-pentaoxaoctadecan-18-oic acid
  参考文献：
  名称：

  用于前列腺癌细胞靶向基因沉默的 KUE-siRNA 偶联物的合成

  摘要：

  KUE-siRNA偶联物是基于炔丙基终止的 siRNA 和赖氨酸-脲-谷氨酸 (KUE) 配体构建的。这些 siRNA 偶联物可以选择性地进入表达前列腺特异性膜抗原 (PSMA) 的前列腺癌细胞以介导特定基因的敲除。

  DOI：

  10.1002/cbic.202100243

文献信息

• [EN] COMPOSITION AND METHOD FOR MODIFYING POLYPEPTIDES<br/>[FR] COMPOSITION ET PROCÉDÉ POUR MODIFIER DES POLYPEPTIDES
  申请人：ADVANCED PROTEOME THERAPEUTICS INC

  公开号：WO2019090242A1

  公开（公告）日：2019-05-09

  The present disclosure provides methods for site-selectively crosslinking payloads to antibodies and other proteins. This can be accomplished using traceless affinity labels designed to label target proteins with bio-orthogonally reactive entities (ORE) using the compositions and methods described herein.

  本公开提供了一种将荷载物与抗体和其他蛋白质进行位点选择性交联的方法。这可以通过使用无痕亲和标签来实现，设计这些标签可以使用生物正交反应实体（ORE）标记目标蛋白质，使用本文描述的组合物和方法。
• [EN] CYCLIC-AMP RESPONSE ELEMENT BINDING PROTEIN (CBP) AND/OR ADENOVIRAL E1A BINDING PROTEIN OF 300 KDA (P300) DEGRADATION COMPOUNDS AND METHODS OF USE<br/>[FR] PROTÉINE DE LIAISON D'ÉLÉMENT DE RÉPONSE AMP CYCLIQUE (CBP) ET/OU PROTÉINE DE LIAISON ADÉNOVIRALE E1A DE COMPOSÉS DE DÉGRADATION DE 300 KDA (P300) ET PROCÉDÉS D'UTILISATION
  申请人：CULLGEN SHANGHAI INC

  公开号：WO2020173440A1

  公开（公告）日：2020-09-03

  Bivalent compounds composition comprises one or more of the bivalent compounds. The bivalent compound comprises a cyclic-AMP response element binding protein (CBP) and/or adenoviral E1A binding protein of 300kDa (P300) ligand (CBP/P300 ligand) conjugated to a degradation tag. The method of using the bivalent compounds is treating certain disease in a subject in need thereof. The method of identifying such bivalent compounds is disclosed.

  二价化合物组合物包括一个或多个二价化合物。二价化合物包括与降解标签共轭的环磷酸腺苷反应元件结合蛋白（CBP）和/或300kDa的腺病毒E1A结合蛋白（P300）配体（CBP/P300配体）。使用二价化合物的方法是治疗需要治疗的受试者的某些疾病。识别此类二价化合物的方法已公开。
• [EN] BIFUNCTIONAL COMPOUNDS COMPRISING APCIN-A AND THEIR USE IN THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS BIFONCTIONNELS COMPRENANT DE L'APCIN-A ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：UNIV NORTHWESTERN

  公开号：WO2020214555A1

  公开（公告）日：2020-10-22

  Described herein are compounds of Formula I, or their pharmaceutically acceptable salts thereof, compositions comprising the same, and methods of using such compounds or compositions in inducing Cdc20 degradation in a cell, blocking mitotic progression, inhibiting tumor proliferation, treating cancer, and/or re-sensitizing a subject to cancer treatment with tamoxifen.

  本文描述了式I的化合物，或其药学上可接受的盐，包含这些化合物的组合物，以及使用这些化合物或组合物在细胞中诱导Cdc20降解、阻止有丝分裂进展、抑制肿瘤增殖、治疗癌症，并/或使受试者对他莫昔芬癌症治疗重新敏感的方法。
• MULTIMERIC BICYCLIC PEPTIDE LIGANDS
  申请人：BicycleTx Limited

  公开号：US20190263866A1

  公开（公告）日：2019-08-29

  The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders and activators of CD137. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by CD137.

  本发明涉及多聚肽的分子支架，其中两个或更多肽环被支架的连接点连接。本发明还描述了通过各种化学连接剂和长度和刚度不同的铰链来多聚肽，使用肽链中的不同连接点。特别地，本发明描述了高亲和力结合和激活CD137的多聚肽。本发明还包括药物结合物，包括所述肽的结合物，与一个或多个效应物和/或功能基团结合，以及包括所述肽配体和药物结合物的制药组合物，并且在预防、抑制或治疗由CD137介导的疾病或障碍中使用所述肽配体和药物结合物。
• PEAMOtecan, a novel chronotherapeutic polymeric drug for brain cancer
  作者：Jasmine Allen、Juan Wang、Olga Yu Zolotarskaya、Amrita Sule、Sajjad Mohammad、Shukaib Arslan、Kenneth J. Wynne、Hu Yang、Kristoffer Valerie

  DOI：10.1016/j.jconrel.2020.02.003

  日期：2020.5

  Glioblastoma multiforme (GBM) is an aggressive and difficult to treat form of brain cancer. In this work, we report on a novel chronotherapeutic polymeric drug, PEAMOtecan, for GBM therapy. PEAMOtecan was synthesized by conjugating camptothecin, a topoisomerase I inhibitor, to our proprietary, 'clickable' and modular polyoxetane polymer platform consisting of acetylene-functionalized 3-ethyl-3-(hydroxymethyl)oxetane (EAMO) repeat units (Patent No.: US 9,421,276) via the linker 3,3'-dithiodipropionic acid (DDPA) with a disulfide bond (S-S) extended by short-chain polyethylene glycol (PEG). We show that PEAMOtecan is a highly modular polymer nanoformulation that protects covalently bound CPT until slowly being released over extended periods of time dependent on the cleavage of the disulfide and ester linkages. PEAMOtecan kills glioma cells by mitotic catastrophe with p53 mutant/knockdown cells being more sensitive than matched wild type cells potentially providing cancer-specific targeting. To establish proof-of-principle therapeutic effects, we tested PEAMOtecan as monotherapy for efficacy in a mouse orthotopic glioma model. PEAMOtecan was administered by one-time, convection-enhanced delivery (CED) intra-tumorally to achieve superior distribution and extended drug release over time. In addition, the near-infrared (NIR) dye Cy5.5 was coupled to the polymer providing live-animal imaging capability to track tissue distribution and clearance of the injected polymer over time. We show that PEAMOtecan significantly improves the survival of mice harboring infra-cranial tumors (p = .0074 compared to untreated group). Altogether, these results support further development and testing of our nano-conjugate platform.