胆固醇杂质35 | 64907-21-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 胆固醇杂质35
• 英文名称: 7beta,25-Dihydroxycholesterol
• 英文别名: cholest-5-ene-3β,7β,25-triol；5-cholesten-3β,7β,25-triol；7β,25-dihydroxycholesterol；(3S,7R,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol
• CAS: 64907-21-7
• 化学式: C₂₇H₄₆O₃
• 分子量: 418.66
• InChiKey: BQMSKLCEWBSPPY-CGSQRZAOSA-N

物化性质

• 沸点：
  548.5±35.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

制备方法与用途

7β,25-二羟基胆固醇是一种内源性代谢物，被发现能够作为表达EBI2的免疫细胞的化学趋化因子。

反应信息

• 作为反应物：
  描述：

  胆固醇杂质35 在 cholesterol 25-hydroxylase 作用下， 生成 7-oxo-cholest-5-ene-3β,25-diol
  参考文献：
  名称：

  11β-羟基类固醇脱氢酶1和2对氧固醇7β，25-二羟基胆固醇和7-酮，25-羟基胆固醇的酶促转化。

  摘要：

  氧固醇是通过自氧化或酶促过程衍生的胆固醇代谢产物。它们由大量的生物活性脂质组成，这些脂质与多种疾病的进展有关。为了阐明涉及氧固醇的（病理）生理机制，阐明氧固醇的潜在形成和降解至关重要。已经报道了11β-羟基类固醇脱氢酶（11β-HSDs）通过催化7-酮胆固醇（7kC）和7β-羟基胆固醇（7βOHC）的相互转化而在氧固醇代谢中的作用。本研究解决了11β-HSD1在从7-酮，25-羟基胆固醇（7k25OHC）酶促生成7β，25-二羟基胆固醇（7β25OHC）中的功能，并测试了11β-HSD2是否能够催化逆反应。第一次使用重组酶，可以证明胆固醇25-羟化酶（CH25H）从7kC形成7k25OHC，以及人和小鼠11β-HSD1进一步立体定向氧化还原成7β25OHC。另外，使用人11β-HSD2的实验显示7β25OHC氧化为7k25OHC。分子建模为7β25OHC和7k25OHC的立体定向互变提供了

  DOI：

  10.1016/j.jsbmb.2019.03.011
• 作为产物：
  描述：

  25-羟基胆甾醇 在 吡啶 、 甲醇 、 叔丁基过氧化氢 、 sodium tetrahydroborate 、 cerium(III) chloride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 103.5h， 生成 胆固醇杂质35
  参考文献：
  名称：

  生物活性氧固醇的氟类似物：具有增强的代谢稳定性的EBI2激动剂的合成

  摘要：

  讨论了几种7-羟基氧固醇的合成及其在先天和适应性免疫应答中作为信号分子的潜在作用。描述了一种新型的氟化合成类似物7α，25-二羟基胆固醇的发现-GPR 183（EBI2）的内源性配体，GPR 183是一种在爱泼斯坦-巴尔病毒感染后高度表达的G蛋白偶联受体。氟氧固醇12表现出良好的代谢稳定性，同时保持了出色的EBI2激动剂活性。

  DOI：

  10.1016/j.bmcl.2016.09.029

文献信息

• NANOMATERIALS
  申请人：Guide Therapeutics, Inc.

  公开号：US20210169804A1

  公开（公告）日：2021-06-10

  Lipid nanoparticle compositions for delivery of nucleic acids are described. The lipid nanoparticle may contain a conformationally constrained ionizable lipid as part of the composition. These compositions may allow for delivery of cargo without the need for a targeting ligand.

  描述了用于传递核酸的脂质纳米粒子组合物。脂质纳米粒子可能包含作为组合物的一部分的构象受限的可离子化脂质。这些组合物可能允许传递货物而无需靶向配体。
• Oxysterols direct B-cell migration through EBI2
  作者：Changlu Liu、Xia V. Yang、Jiejun Wu、Chester Kuei、Neelakandha S. Mani、Li Zhang、Jingxue Yu、Steven W. Sutton、Ning Qin、Homayon Banie、Lars Karlsson、Siquan Sun、Timothy W. Lovenberg

  DOI：10.1038/nature10226

  日期：2011.7

  The EBI2 receptor (Epstein–Barr virus-induced gene 2, also known as GPR183) was recently shown to be linked to autoimmune disease, and is a critical regulator of the humoral immune response. It is a G-protein-coupled receptor, and its natural ligand has been unknown. Two groups now bring an end to the 'orphan' status of this receptor with identification of specific oxysterols as its natural ligands. The most potent ligand and activator is 7a,25-dihydroxycholesterol, and the EBI2–oxysterol signalling pathway has an important role in the adaptive immune response. EBI2 (also called GPR183) is an orphan G-protein-coupled receptor that is highly expressed in spleen and upregulated upon Epstein–Barr-virus infection1. Recent studies indicated that this receptor controls follicular B-cell migration and T-cell-dependent antibody production2,3,4,5,6. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol metabolism7,8,9. The biological effects of oxysterols have largely been credited to the activation of nuclear hormone receptors10,11. Here we isolate oxysterols from porcine spleen extracts and show that they are endogenous ligands for EBI2. The most potent ligand and activator is 7α,25-dihydroxycholesterol (OHC), with a dissociation constant of 450 pM for EBI2. In vitro, 7α,25-OHC stimulated the migration of EBI2-expressing mouse B and T cells with half-maximum effective concentration values around 500 pM, but had no effect on EBI2-deficient cells. In vivo, EBI2-deficient B cells or normal B cells desensitized by 7α,25-OHC pre-treatment showed reduced homing to follicular areas of the spleen. Blocking the synthesis of 7α,25-OHC in vivo with clotrimazole, a CYP7B1 inhibitor, reduced the content of 7α,25-OHC in the mouse spleen and promoted the migration of adoptively transferred pre-activated B cells to the T/B boundary (the boundary between the T-zone and B-zone in the spleen follicle), mimicking the phenotype of pre-activated B cells from EBI2-deficient mice. Our results show an unexpected causal link between EBI2, an orphan G-protein-coupled receptor controlling B-cell migration, and the known immunological effects of certain oxysterols, thus uncovering a previously unknown role for this class of molecules.

  克霉唑，可阻止体内7α，25-二羟基胆固醇的合成。
• [EN] NANOMATERIALS COMPRISING ESTER-LINKED ACETALS<br/>[FR] NANOMATÉRIAUX COMPRENANT DES ACÉTALS À LIAISON ESTER
  申请人：BEAM THERAPEUTICS INC

  公开号：WO2022140252A1

  公开（公告）日：2022-06-30

  The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use.

  本公开说明书描述了组合物、制剂、纳米颗粒（如脂质纳米颗粒）和/或纳米材料及其使用方法。
• [EN] NANOMATERIALS COMPRISING CARBONATES<br/>[FR] NANOMATÉRIAUX COMPRENANT DES CARBONATES
  申请人：BEAM THERAPEUTICS INC

  公开号：WO2022140239A1

  公开（公告）日：2022-06-30

  The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use.

  本公开说明书描述了组合物、制备、纳米颗粒（如脂质纳米颗粒）和/或纳米材料及其使用方法。
• [EN] NANOMATERIALS COMPRISING ACETALS<br/>[FR] NANOMATÉRIAUX COMPRENANT DES ACÉTALS
  申请人：BEAM THERAPEUTICS INC

  公开号：WO2022140238A1

  公开（公告）日：2022-06-30

  The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use.

  本公开说明书描述了组成物、制备、纳米粒子（如脂质纳米粒子）和/或纳米材料及其使用方法。