(4Z,7S,8R,9E,11E,13Z,15E,17S,19Z)-7,8,17-三羟基-4,9,11,13,15,19-二十二碳六烯酸 | 872993-05-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (4Z,7S,8R,9E,11E,13Z,15E,17S,19Z)-7,8,17-三羟基-4,9,11,13,15,19-二十二碳六烯酸
• 英文名称: 7,8,17-Trihydroxydocosa-4,9,11,13,15,19-hexaenoic acid
• CAS: 872993-05-0
• 化学式: C₂₂H₃₂O₅
• 分子量: 376.5
• InChiKey: OIWTWACQMDFHJG-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：50 mg/ml；乙醇：50 mg/ml； PBS（pH 7.2）：0.05 mg/ml
• 碰撞截面：
  198.2 Ų [M-H]-; 196.6 Ų [M+Na]+

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  98
• 氢给体数：
  4
• 氢受体数：
  5

制备方法与用途

生物活性

Resolvin D1 (RvD1) 是一种炎症的内源性促分解介质，衍生自急性炎症缓解阶段的 omega-3 二十二碳六烯酸。它通过调节肌动蛋白聚合来阻止促炎性中性粒细胞迁移，减少巨噬细胞中的 TNF-α 介导的炎症，并增强巨噬细胞对凋亡细胞的吞噬作用。

靶点

Human Endogenous Metabolite

体外研究

Resolvin D1 (RvD1)（1-100 nM；15 分钟）诱导原代人巨噬细胞发生剂量依赖性的短期功能变化。RvD1 引起细胞内 Ca²⁺ 释放，阻断趋化性迁移，并在 10 nM 浓度下刺激微生物颗粒的吞噬作用。

Resolvin D1（0-500 nM；72 小时）在 RAW264.7 巨噬细胞中以不同浓度显示出对 LPS 引发的 TRAP 和 cathepsin K 表达的强大抑制作用。

体内研究

Resolvin D1 (RvD1)（100-1000 ng；i.p.；每日 10 天）改善了类风湿性关节炎小鼠的临床终点指标。

动物模型及实验结果

• 动物模型：18-20 克，30 只 8 周龄雌性 DBA/1J 小鼠（胶原抗体诱导性关节炎 (CAIA)）
• 剂量：100、500 和 1000 ng（或每日 4-10 天注射 1000 ng）
• 给药方式：i.p. 注射，每日 10 天
• 结果：表现出关节炎评分降低。

文献信息

• [EN] METHODS AND COMPOSITIONS FOR TREATING CYSTIC FIBROSIS AIRWAYS<br/>[FR] MÉTHODES ET COMPOSITIONS DESTINÉES AU TRAITEMENT DES VOIES RESPIRATOIRES ATTEINTES DE MUCOVISCIDOSE
  申请人：INST NAT SANTE RECH MED

  公开号：WO2020115231A1

  公开（公告）日：2020-06-11

  The present invention relates to resolving D1 (RvD1) compound for use in the treatment of cystic fibrosis. Inventors have performed ex vivo studies on primary cultures of alveolar macrophages and bronchial epithelial cells from children with CF and in human bronchial epithelial cell lines. They have also performed in vivo studies in homozygous F508del-CFTR mice treated with vehicle control or RvD1 (1-100 nM). They have shown that RvD1 increased the CF ASL height in human bronchial epithelium and restored the nasal trans-epithelial potential difference in CF mice by decreasing the amiloride-sensitive Na+ absorption and stimulating CFTR-independent Cl- secretion. They have observed that RvD1 decreased TNFα induced IL-8 secretion and enhanced the phagocytic and bacterial killing capacity of human CF alveolar macrophages. Thus, RvD1 resolves CF airway pathogenesis and has therapeutic potential in CF lung disease.
• [EN] COMPOSITIONS AND METHODS FOR TREATING HEARING LOSS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE PERTE AUDITIVE
  申请人：UNIV CALIFORNIA

  公开号：WO2020132161A1

  公开（公告）日：2020-06-25

  Aspects of the disclosure provide methods and compositions involving extracellular vesicles that can be used to treat hearing loss. Extracellular vesicles are not immunogenic (they do not induce rejection or inflammatory responses), are easily incorporated by other cells, and lack of the limitations associated with the delivery of intact cells. Furthermore, it was discovered that exosome comprise or can be stimulated to comprise pro-resolution mediators and precursors that allow for the activation of endogenous hearing protection mechanisms rather than inhibition of natural defense processes. Accordingly, aspects of the disclosure relate to a method for treating, preventing, or delaying the onset of hearing loss, the method comprising administering a composition comprising extracellular vesicles to the ear of the subject.