[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-methoxy-2-(methoxymethyl)oxolan-3-yl] [(2R,3S)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核糖核苷3'-磷酸盐
• 英文名称: [(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-methoxy-2-(methoxymethyl)oxolan-3-yl] [(2R,3S)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate
• 化学式: C₁₆H₂₅N₂O₁₁P
• 分子量: 452.35
• InChiKey: LKRCOZHZAPPTSJ-MRIXOBAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  11

文献信息

• SHORT INTERFERING NUCLEIC ACID (siNA) MOLECULES CONTAINING A 2' INTERNUCLEOSIDE LINKAGE
  申请人：Chang Wonsuk

  公开号：US20160068837A1

  公开（公告）日：2016-03-10

  The present invention relates to RNAi molecules, and compositions thereof, comprising a 2′ internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5′ end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5′ modified nucleotides that comprise, among other potential modifications, a 2′ internucleoside linkage. The invention further relates to 5′ modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

  本发明涉及RNAi分子及其组成物，包括连接在反义链5'端的位置1核苷酸和位置2核苷酸之间的2'间核苷酸连接。具体而言，本发明涉及能够介导RNA干扰的单链和双链短干扰核酸（siNA）分子，其包含5'修饰核苷酸，其中包括2'间核苷酸连接等其他潜在修饰。本发明还涉及用作试剂的5'修饰核苷酸，用于生成本发明的RNAi分子以及使用所述RNAi分子的方法。
• Systemic delivery of myostatin short interfering nucleic acids (siNA) conjugated to a lipophilic moiety
  申请人：SIRNA THERAPEUTICS, INC.

  公开号：US10004814B2

  公开（公告）日：2018-06-26

  The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.

  本发明提供的方法包括体内递送能够介导 RNA 干扰并减少肌生长抑素表达的小核酸分子，其中小核酸分子通过全身给药导入受试者。具体而言，本发明涉及的方法包括体内递送靶向受试者表达的肌生长蛋白基因的短干扰核酸（siNA）分子，其中 siNA 分子与亲脂分子（如胆固醇）共轭。按照所公开的方法递送的肌生长抑素 siNA 共轭物可用于调节肌生长抑素的体内表达，增加肌肉质量和/或提高肌肉性能。所公开方法的使用还可用于治疗肌肉骨骼疾病或失调，和/或导致肌肉受到不利影响的疾病或失调。
• Short interfering nucleic acid (siNA) molecules containing a 2′ internucleoside linkage (3dT)
  申请人：SIRNA THERAPEUTICS, INC.

  公开号：US10738308B2

  公开（公告）日：2020-08-11

  The present invention relates to RNAi molecules, and compositions thereof, comprising a 2′ internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5′ end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5′ modified nucleotides that comprise, among other potential modifications, a 2′ internucleoside linkage. The invention further relates to 5′ modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

  本发明涉及RNAi分子及其组合物，其包含连接反义链5′端的1位核苷酸和2位核苷酸的2′核苷间连接。具体地说，本发明涉及能够介导 RNA 干扰的单链和双链短干扰核酸（siNA）分子，这些分子包含 5′修饰的核苷酸，这些核苷酸除其他可能的修饰外，还包含 2′核苷间连接。本发明进一步涉及用作试剂生成本发明 RNAi 分子的 5′修饰核苷酸以及使用所公开 RNAi 分子的方法。
• SHORT INTERFERING NUCLEIC ACID (SINA) MOLECULES CONTAINING A 2' INTERNUCLEOSIDE LINKAGE
  申请人：Sirna Therapeutics, Inc.

  公开号：EP2958998B1

  公开（公告）日：2017-12-27
• SYSTEMIC DELIVERY OF MYOSTATIN SHORT INTERFERING NUCLEIC ACIDS (siNA) CONJUGATED TO A LIPOPHILIC MOIETY
  申请人：SEPP-LORENZINO Laura

  公开号：US20160256570A1

  公开（公告）日：2016-09-08

  The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.