2-Naphthacenecarboxylic acid, 6,6a,7,10,10a,11-hexahydro-6a,7,10a,12-tetrahydroxy-3,8-dimethoxy-1-methyl-6,10,11-trioxo-, methyl ester | 146864-75-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 英文名称: 2-Naphthacenecarboxylic acid, 6,6a,7,10,10a,11-hexahydro-6a,7,10a,12-tetrahydroxy-3,8-dimethoxy-1-methyl-6,10,11-trioxo-, methyl ester
• 英文别名: methyl 6a,7,10a,12-tetrahydroxy-3,8-dimethoxy-1-methyl-6,10,11-trioxo-7H-tetracene-2-carboxylate
• CAS: 146864-75-7
• 化学式: C₂₃H₂₀O₁₁
• 分子量: 472.4
• InChiKey: ULHJWHCSSAEMLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  177
• 氢给体数：
  4
• 氢受体数：
  11

文献信息

• Compounds and methods for enhancing delivery of free polynucleotide
  申请人：——

  公开号：US20040009947A1

  公开（公告）日：2004-01-15

  The discovery of simple, nontoxic, and pharmaceutically defined methods for genetic modification of cells and tissues would enable development of a variety of molecular medicines. “Free”, ‘direct’, or ‘naked’ polynucleotide administration is a simple, apparently safe, and pharmaceutically defined polynucleotide delivery method. Murine, macaque, and clinical human experiments have demonstrated transfection of various tissues, such as respiratory tissues, after direct application of ‘free’ polynucleotide. However, direct DNA transfection is relatively inefficient in comparison to many transduction systems. The invention herein is directed to transfection enhancing agents which augment the transfection activity of ‘free’ polynucleotide, thereby facilitating the development of simple and safe alternatives to tissue transfection, more particularly respiratory tissue transfection. The experiments described herein indicate that nucleases, both extra- and intra-cellular, present in many biological fluids, such as respiratory fluid, accelerate clearance of biologically active plasmid from the tissue, and that co-administration of a nuclease inhibitor together with free polynucleotide results in marked enhancement of expression of the polynucleotide of interest. These findings support the disclosed invention of an improved polynucleotide delivery system, a ‘free’ plasmid-based transfection technology.

  发现简单、无毒和药学定义的细胞和组织基因修饰方法将有助于开发各种分子药物。游离"、"直接 "或 "裸体 "多核苷酸给药是一种简单、明显安全和药学定义的多核苷酸给药方法。小鼠、猕猴和临床人体实验表明，直接应用 "游离 "多核苷酸可转染各种组织，如呼吸道组织。然而，与许多转导系统相比，直接 DNA 转染的效率相对较低。本发明针对的是增强 "游离 "多核苷酸转染活性的转染增强剂，从而促进了组织转染，特别是呼吸道组织转染的简单安全替代品的开发。本文所述的实验表明，存在于许多生物液体（如呼吸液）中的细胞外和细胞内核酸酶会加速组织中生物活性质粒的清除，而核酸酶抑制剂与游离多核苷酸同时使用会显著增强相关多核苷酸的表达。这些发现支持了已公开的改进型多核苷酸递送系统的发明，即一种基于 "游离 "质粒的转染技术。