2-linoleyoloxyl-3-linoleyloxyl-1-N,N-dimethylaminoproprane | 1019000-51-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-linoleyoloxyl-3-linoleyloxyl-1-N,N-dimethylaminoproprane
• 英文别名: octadeca-9,12-dienoic acid 3-dimethyl amino-2-octadeca-9,12-dienoyloxy-propyl ester；1,2-dilinoleoyl-3-dimethylaminopropane；DLinDAP；[3-(dimethylamino)-2-[(9Z,12Z)-octadeca-9,12-dienoyl]oxypropyl] (9Z,12Z)-octadeca-9,12-dienoate
• CAS: 1019000-51-1
• 化学式: C₄₁H₇₃NO₄
• 分子量: 644.035
• InChiKey: HCAJCMUKLZSPFT-KWXKLSQISA-N

物化性质

• 沸点：
  668.5±55.0 °C(Predicted)
• 密度：
  0.927±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  13.7
• 重原子数：
  46
• 可旋转键数：
  35
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

制备方法与用途

DLinDAP是一种可电离的阳离子脂质，常用于siRNA的递送。

反应信息

• 作为产物：
  描述：

  3-二甲胺基-1,2-丙二醇 在 吡啶 、 sodium hydride 、 溶剂黄146 作用下， 以 吡啶 、 水 、 苯 为溶剂， 反应 49.5h， 生成 2-linoleyoloxyl-3-linoleyloxyl-1-N,N-dimethylaminoproprane
  参考文献：
  名称：

  IMPROVED COMPOSITIONS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS

  摘要：

  公开号：

  EP2224912B1

文献信息

• [EN] CATIONIC LIPIDS COMPRISING AN HYDROXY MOIETY<br/>[FR] LIPIDES CATIONIQUES COMPRENANT UNE FRACTION HYDROXY
  申请人：TRANSLATE BIO INC

  公开号：WO2020257611A1

  公开（公告）日：2020-12-24

  Disclosed are lipids which are compounds of Formula I. Lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

  本文披露的是化合物I的脂质。本文提供的脂质可用于传递和表达mRNA和编码蛋白，例如作为脂质体传递载体的组分，因此可用于治疗与一种或多种蛋白质缺乏相关的各种疾病、紊乱和症状。
• SILENCING OF POLO-LIKE KINASE EXPRESSION USING INTERFERING RNA
  申请人：PROTIVA BIOTHERAPEUTICS, INC.

  公开号：US20160115483A1

  公开（公告）日：2016-04-28

  The present invention provides compositions comprising interfering RNA (e.g., siRNA, aiRNA, miRNA) that target polo-like kinase 1 (PLK-1) expression and methods of using such compositions to silence PLK-1 expression. More particularly, the present invention provides unmodified and chemically modified interfering RNA molecules which silence PLK-1 expression and methods of use thereof. The present invention also provides serum-stable nucleic acid-lipid particles (e.g., SNALP) comprising an interfering RNA molecule described herein, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing PLK-1 gene expression by administering an interfering RNA molecule described herein to a mammalian subject. The present invention additionally provides methods of identifying and/or modifying PLK-1 interfering RNA having immunostimulatory properties. Methods for sensitizing a cell such as a cancer cell to the effects of a chemotherapy drug comprising sequentially delivering PLK-1 interfering RNA followed by the chemotherapy drug are also provided.

  本发明提供了包含干扰RNA（例如siRNA、aiRNA、miRNA）的组合物，其靶向波洛样激酶1（PLK-1）表达，并提供了使用这种组合物来沉默PLK-1表达的方法。更具体地说，本发明提供了未修饰和化学修饰的干扰RNA分子，这些分子可以沉默PLK-1表达，并提供了它们的使用方法。本发明还提供了含有干扰RNA分子、阳离子脂质和非阳离子脂质的血清稳定核酸-脂质颗粒（例如SNALP），这些颗粒还可以进一步包含抑制颗粒聚集的共轭脂质。本发明还提供了通过向哺乳动物主体施用本文描述的干扰RNA分子来沉默PLK-1基因表达的方法。本发明还提供了识别和/或修改具有免疫刺激性能的PLK-1干扰RNA的方法。此外，还提供了一种通过顺序输送PLK-1干扰RNA后接着化疗药物来使细胞（如癌细胞）对化疗药物产生敏感性的方法。
• CORONAVIRUS VACCINE
  申请人：BioNTech RNA Pharmaceuticals GmbH

  公开号：EP3901261A1

  公开（公告）日：2021-10-27

  This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

  该披露涉及RNA领域，用于预防或治疗冠状病毒感染。具体来说，本披露涉及用于预防冠状病毒感染和诱导有效的冠状病毒抗原特异性免疫应答（如抗体和/或T细胞应答）的方法和药剂。具体而言，在一种实施方式中，本披露涉及通过向受试者给予编码SARS-CoV-2尖刺蛋白（S蛋白）表位的肽或蛋白的RNA来诱导免疫应答，特别是在受试者中诱导对冠状病毒S蛋白的免疫应答，即编码疫苗抗原的疫苗RNA。
• [EN] COMPOSITION AND METHODS FOR TREATMENT OF PRIMARY CILIARY DYSKINESIA<br/>[FR] COMPOSITION ET MÉTHODES DE TRAITEMENT D'UNE DYSKINÉSIE CILIAIRE PRIMITIVE
  申请人：TRANSLATE BIO INC

  公开号：WO2021226463A1

  公开（公告）日：2021-11-11

  The present invention provides, among other things, methods and compositions for treating primary ciliary dyskinesia (PCD) based on mRNA therapy. The compositions used in treatment of PCD comprise an mRNA comprising a dynein axonemal intermediate chain 1 (DNAI1) coding sequence and are administered at an effective dose and an administration interval such that at least one symptom or feature of PCD is reduced in intensity, severity, or frequency or has a delayed onset. mRNAs with optimized DNAI1 coding sequences are provided that can be administered without the need for modifying the nucleotides of the mRNA to achieve sustained in vivo function.

  本发明提供了治疗原发性纤毛运动障碍（PCD）的方法和组合物，基于mRNA疗法。用于治疗PCD的组合物包括一个包含动力蛋白纤毛中间链1（DNAI1）编码序列的mRNA，以有效剂量和给药间隔进行给药，以使PCD的至少一个症状或特征在强度、严重程度、频率上减轻，或延迟发作。提供了具有优化DNAI1编码序列的mRNA，可以在不需要修改mRNA核苷酸的情况下进行给药，以实现体内持续功能。
• [EN] AMINO LIPID BASED IMPROVED LIPID FORMULATION<br/>[FR] FORMULATION LIPIDIQUE AMÉLIORÉE À BASE D'AMINO LIPIDE
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2009132131A1

  公开（公告）日：2009-10-29

  The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic aicd to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art. Formulae (I), (II), (III), (IV).

  本发明提供了将治疗剂传递给细胞的组合物和方法。特别是，这些包括新型脂质和核酸-脂质颗粒，它们能够高效地封装核酸并将封装的核酸有效地传递到体内细胞中。本发明的组合物非常强效，因此可以在相对较低的剂量下有效地降低特定靶蛋白的表达。此外，与先前已知的技术中的组合物和方法相比，本发明的组合物和方法毒性更低，疗效指数更高。公式（I）、（II）、（III）、（IV）。