N-[1-[(2R,3R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methoxyoxolan-2-yl]-2-oxopyrimidin-4-yl]acetamide

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: N-[1-[(2R,3R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methoxyoxolan-2-yl]-2-oxopyrimidin-4-yl]acetamide
• 化学式: C₁₂H₁₇N₃O₆
• 分子量: 299.28
• InChiKey: CYDFBLGNJUNSCC-APHKKCJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  6

文献信息

• [EN] LINKER COMPOUNDS<br/>[FR] COMPOSÉS DE LIAISON
  申请人：MPEG LA L L C

  公开号：WO2021226454A1

  公开（公告）日：2021-11-11

  Linker compounds, methods of making them, and methods of using them as linking agents for oligonucleotides and other chemical and biological substances are described. Embodiments of linker compounds are configured or selected to exhibit higher stability to cleavage by serum nucleases relative to intracellular nucleases, enabling enhanced control of longevity and hence bioavailability to a target cell of the chemical and biological substances linked together by such linker compounds when administered to a subject.

  本文描述了连接剂化合物、制备方法以及将它们用作寡核苷酸和其他化学和生物物质的连接剂的使用方法。连接剂化合物的实施例被配置或选择以相对于细胞内核酸酶具有更高的稳定性，从而使得通过这种连接剂化合物连接在一起并在给予受试者时可控制生物和化学物质的寿命和因此生物可用性增强到目标细胞。
• MRNA combination therapy for the treatment of cancer
  申请人：ModernaTX, Inc.

  公开号：US10335486B2

  公开（公告）日：2019-07-02

  The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.

  本公开涉及使用核酸（如mRNA）组合疗法治疗癌症。本公开提供了组合物及其制备、制造和治疗使用的方法，其中这些组合物包括至少两种组合在一起的多核苷酸（如mRNA），其中至少两种多核苷酸选自由以下组成的组(i)编码免疫应答引物的多核苷酸（如IL23），(ii)编码免疫应答引物的多核苷酸（如IL23），(iii)编码免疫应答引物的多核苷酸（如IL23），(iv)编码免疫应答引物的多核苷酸（如IL23）、IL23），(ii) 编码免疫应答共刺激信号（如 OX40L）的多核苷酸，(iii) 编码检查点抑制剂（如抗 CTLA-4 抗体）的多核苷酸，以及 (iv) 其组合。本文公开的治疗方法包括，例如，在有需要的受试者中施用本文公开的用于治疗癌症的组合疗法，例如，通过减小肿瘤大小或抑制肿瘤生长。在某些方面，本文公开的组合疗法是肿瘤内给药。
• Multimeric oligonucleotides having decreased kidney clearance
  申请人：MPEG LA, LLC

  公开号：US11078484B2

  公开（公告）日：2021-08-03

  The present invention relates to methods of administering to a subject multimeric oligonucleotides having monomeric subunits joined by linkers. The multimeric oligonucleotides have a molecular weight of at least about 45 kD and other characteristics, such that their clearance due to glomerular filtration is reduced. The present invention also relates to such multimeric oligonucleotides and methods of synthesizing such multimeric oligonucleotides.

  本发明涉及向受试者施用具有通过连接体连接的单体亚基的多聚物寡核苷酸的方法。这些多聚物寡核苷酸的分子量至少约为 45 kD，并具有其他特征，从而减少了它们因肾小球滤过而产生的清除率。本发明还涉及这种多聚物寡核苷酸和合成这种多聚物寡核苷酸的方法。
• Defined multi-conjugate oligonucleotides
  申请人：MPEG LA, LLC

  公开号：US11352629B2

  公开（公告）日：2022-06-07

  Defined multi-conjugate oligonucleotides can have predetermined sizes and compositions. For example, in various embodiment, defined multi-conjugate oligonucleotides can have advantageous properties, for example in the form of defined multi-conjugate siRNA (i.e., including two, three or more siRNA) having enhanced intracellular delivery and/or multi-gene silencing effects. In various embodiment, the defined multi-conjugate oligonucleotides can be synthesized via new synthetic intermediates and methods. The defined multi-conjugate oligonucleotides can be used, for example, in reducing gene expression, biological research, treating or preventing medical conditions, or to produce new or altered phenotypes in cells or organisms.

  定义的多共轭寡核苷酸可以具有预定的大小和组成。例如，在不同的实施方案中，定义的多共轭寡核苷酸可以具有优势特性，例如以定义的多共轭 siRNA（即包括两个、三个或更多 siRNA）的形式，具有增强的细胞内递送和/或多基因沉默效应。在不同的实施方案中，定义的多共轭寡核苷酸可通过新的合成中间体和方法合成。所定义的多共轭寡核苷酸可用于减少基因表达、生物研究、治疗或预防医疗状况，或在细胞或生物体中产生新的或改变的表型。
• MULTIMERIC OLIGONUCLEOTIDES HAVING DECREASED KIDNEY CLEARANCE
  申请人：MPEG LA, LLC

  公开号：US20180223284A1

  公开（公告）日：2018-08-09

  The present invention relates to methods of administering to a subject multimeric oligonucleotides having monomeric subunits joined by linkers. The multimeric oligonucleotides have a molecular weight of at least about 45 kD and other characteristics, such that their clearance due to glomerular filtration is reduced. The present invention also relates to such multimeric oligonucleotides and methods of synthesizing such multimeric oligonucleotides.