3β-hydroxy-7-oxocholest-5-en-26-oic acid | 1246298-64-5

• 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
• 英文名称: 3β-hydroxy-7-oxocholest-5-en-26-oic acid
• 英文别名: 3β-hydroxy-5-cholesten-7-one-26-oic acid；7KCh-27COOH；(25R)-3beta-hydroxycholest-5-en-7-one-26-oic acid；(2R,6R)-6-[(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-7-oxo-1,2,3,4,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]-2-methylheptanoic acid
• CAS: 1246298-64-5
• 化学式: C₂₇H₄₂O₄
• 分子量: 430.628
• InChiKey: QOEPZHFZXUROGV-BXDHRDAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-7-oxocholest-5-en-26-oic acid 在 cerium(III) chloride 、 硼氘化钠 、 氘代甲醇-d 作用下， 生成 [7β-(2H)]3β,7α-dihydroxycholest-5-en-26-oic acid 、 [7α-(2H)]3α,7β-dihydroxycholest-5-en-26-oic acid
  参考文献：
  名称：

  [EN] DEUTERATED COMPOUNDS
  [FR] COMPOSÉS DEUTÉRÉS

  摘要：

  通式为（I）的化合物其中（I）R1-R4各自独立地选择H和氘; 并且R1-R4中至少有一个是氘。已发现这些化合物在治疗神经退行性疾病，尤其是运动神经元疾病等方面特别有用。

  公开号：

  WO2015036726A1
• 作为产物：
  描述：

  5-胆甾烯-3β-醇-7-酮 在 isocitrate dehydrogenase 、 adrenodoxin 、 乙二胺四乙酸 、 adrenodoxin reductase 、 cytochrome P₄₅₀ 27A₁ 、 NADPH 、 trisodium isocitrate 作用下， 反应 0.08h， 生成 3β-hydroxy-7-oxocholest-5-en-26-oic acid 、 3,27-二羟基-5-胆甾烯-7-酮
  参考文献：
  名称：

  Conversion of 7-ketocholesterol to oxysterol metabolites by recombinant CYP27A1 and retinal pigment epithelial cells

  摘要：

  Of the different oxygenated cholesterol metabolites, 7-ketocholesterol (7KCh) is considered a noxious oxysterol implicated in the development of certain pathologies, including those found in the eye. Here we elucidated whether sterol 27-hydroxylase cytochrome P450 27A1 (CYP27A1) is involved in elimination of 7KCh from the posterior part of the eye: the neural retina and underlying retinal pigment epithelium (RPE). We first established that the affinities of purified recombinant CYP27A1 for 7KCh and its endogenous substrate cholesterol are similar, yet 7KCh is metabolized at a 4-fold higher rate than cholesterol in the reconstituted system in vitro. Lipid extracts from bovine neural retina and RPE were then analyzed by isotope dilution GC-MS for the presence of the 7KCh-derived oxysterols. Two metabolites, 3 beta,27-dihydroxy-5-cholesten-7-one (7KCh-27OH) and 3 beta-hydroxy-5-cholesten-7-one-26-oic acid (7KCh-27COOH), were detected in the RPE but not in the neural retina. 7KCh-27OH was also formed when RPE homogenates were supplemented with NADPH and the mitochondrial redox system. Quantifications in human RPE showed that CYP27A1 is indeed expressed in the RPE at 2-4-fold higher levels than in the neural retina. The data obtained represent evidence for the role of CYP27A1 in retinal metabolism of 7KCh and suggest that, in addition to cholesterol removal, the functions of this enzyme could also include elimination of toxic endogenous compounds.-Heo, G-Y., I. Bederman, N. Mast, W-L. Liao, I. V. Turko, and I. A. Pikuleva. Conversion of 7-ketocholesterol to oxysterol metabolites by recombinant CYP27A1 and retinal pigment epithelial cells. J. Lipid Res. 2011. 52: 1117-1127.

  DOI：

  10.1194/jlr.m014217

文献信息

• DEUTERATED COMPOUNDS
  申请人：Swansea University

  公开号：EP3044192B1

  公开（公告）日：2017-10-18
• COMPOUND AND METHOD FOR THE TREATMENT AND DIAGNOSIS OF NEURODEGENERATIVE CONDITIONS
  申请人：Swansea University

  公开号：US20210139529A1

  公开（公告）日：2021-05-13

  Pharmaceutical compositions comprising cholestenoic acids and deuterated derivatives thereof, methods of treatment or prevention of neurodegenerative conditions, as well as diagnostic methods and novel biomarkers form aspects of the invention.
• Conversion of 7-ketocholesterol to oxysterol metabolites by recombinant CYP27A1 and retinal pigment epithelial cells
  作者：Gun-Young Heo、Ilya Bederman、Natalia Mast、Wei-Li Liao、Illarion V. Turko、Irina A. Pikuleva

  DOI：10.1194/jlr.m014217

  日期：2011.6

  Of the different oxygenated cholesterol metabolites, 7-ketocholesterol (7KCh) is considered a noxious oxysterol implicated in the development of certain pathologies, including those found in the eye. Here we elucidated whether sterol 27-hydroxylase cytochrome P450 27A1 (CYP27A1) is involved in elimination of 7KCh from the posterior part of the eye: the neural retina and underlying retinal pigment epithelium (RPE). We first established that the affinities of purified recombinant CYP27A1 for 7KCh and its endogenous substrate cholesterol are similar, yet 7KCh is metabolized at a 4-fold higher rate than cholesterol in the reconstituted system in vitro. Lipid extracts from bovine neural retina and RPE were then analyzed by isotope dilution GC-MS for the presence of the 7KCh-derived oxysterols. Two metabolites, 3 beta,27-dihydroxy-5-cholesten-7-one (7KCh-27OH) and 3 beta-hydroxy-5-cholesten-7-one-26-oic acid (7KCh-27COOH), were detected in the RPE but not in the neural retina. 7KCh-27OH was also formed when RPE homogenates were supplemented with NADPH and the mitochondrial redox system. Quantifications in human RPE showed that CYP27A1 is indeed expressed in the RPE at 2-4-fold higher levels than in the neural retina. The data obtained represent evidence for the role of CYP27A1 in retinal metabolism of 7KCh and suggest that, in addition to cholesterol removal, the functions of this enzyme could also include elimination of toxic endogenous compounds.-Heo, G-Y., I. Bederman, N. Mast, W-L. Liao, I. V. Turko, and I. A. Pikuleva. Conversion of 7-ketocholesterol to oxysterol metabolites by recombinant CYP27A1 and retinal pigment epithelial cells. J. Lipid Res. 2011. 52: 1117-1127.
• [EN] DEUTERATED COMPOUNDS<br/>[FR] COMPOSÉS DEUTÉRÉS
  申请人：UNIV SWANSEA

  公开号：WO2015036726A1

  公开（公告）日：2015-03-19

  Compounds of general formula (I) wherein (I) R1 - R4 are each independently selected from H and deuterium; and at least one of R1 - R4 is deuterium. The compounds have been found to be particularly useful for treating neurodegenerative conditions and in particular but not exclusively conditions such as motor neurone disease.

  通式为（I）的化合物其中（I）R1-R4各自独立地选择H和氘; 并且R1-R4中至少有一个是氘。已发现这些化合物在治疗神经退行性疾病，尤其是运动神经元疾病等方面特别有用。