(5Z,8Z,10E,14Z)-12-氧代-5,8,10,14-二十碳四烯酸 | 108437-64-5

• 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: (5Z,8Z,10E,14Z)-12-氧代-5,8,10,14-二十碳四烯酸
• 英文名称: 12-oxo-ETE
• 英文别名: 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid；12-ketoeicosatetraenoic acid；12-oxoeicosatetraenoic acid；(5Z,8Z,10E,14Z)-12-oxoicosa-5,8,10,14-tetraenoic acid
• CAS: 108437-64-5
• 化学式: C₂₀H₃₀O₃
• 分子量: 318.456
• InChiKey: GURBRQGDZZKITB-VXBMJZGYSA-N

物化性质

• 溶解度：
  DMF：可混溶； DMSO：可混溶；乙醇：可混溶； PBS pH 7.2：0.8 mg/mL
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C

制备方法与用途

12-氧酯通过白三烯B4受体或一个共同的激活序列，诱导细胞质游离钙的快速、剂量依赖性的增加。

反应信息

• 作为产物：
  描述：

  花生四烯酸 在 吡啶 、 human platelet 12-lipoxygenase 、 乙酸酐 作用下， 以 aq. buffer 为溶剂， 生成 (5Z,8Z,10E,14Z)-12-氧代-5,8,10,14-二十碳四烯酸
  参考文献：
  名称：

  Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase isozymes

  摘要：

  Oxo-lipids, a large family of oxidized human lipoxygenase (hLOX) products, are of increasing interest to researchers due to their involvement in different inflammatory responses in the cell. Oxo-lipids are unique because they contain electrophilic sites that can potentially form covalent bonds through a Michael addition mechanism with nucleophilic residues in protein active sites and thus increase inhibitor potency. Due to the resemblance of oxo-lipids to LOX substrates, the inhibitor potency of 4 different oxo-lipids; 5-oxo-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE), 12-oxo-5,8,10,14-(Z,Z,E,Z)-eicosatetraenoic acid (12-oxo-ETE), and 13-oxo-9,11-(Z,E)-octadecadienoic acid (13-oxo-ODE) were determined against a library of LOX isozymes; leukocyte 5-lipoxygenase (h5-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), human platelet 12-lipoxygenase (h12-LOX), human epithelial 15-lipoxygenase-2 (h15-LOX-2), soybean 15-lipoxygenase-1 (s15-LOX-1), and rabbit reticulocyte 15-LOX (r15-LOX). 15-Oxo-ETE exhibited the highest potency against h12-LOX, with an IC50 = 1 +/- 0.1 mu M and was highly selective. Steady state inhibition kinetic experiments determined 15-oxo-ETE to be a mixed inhibitor against h12-LOX, with a K-ic value of 0.087 +/- 0.008 mu M and a K-iu value of 2.10 +/- 0.8 mu M. Time-dependent studies demonstrated irreversible inhibition with 12-oxo-ETE and h15-LOX-1, however, the concentration of 12-oxo-ETE required (K-i = 36.8 +/- 13.2 mu M) and the time frame (k(2) = 0.0019 +/- 0.00032 s(-1)) were not biologically relevant. These data are the first observations that oxo-lipids can inhibit LOX isozymes and may be another mechanism in which LOX products regulate LOX activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.05.025

文献信息

• Synthesis of 12-KETE and its 8,9-trans-isomer
  作者：Steven S. Wang、Joshua Rokach、William S. Powell、Catherine Dekle、Steven J. Feinmark

  DOI：10.1016/s0040-4039(00)73109-1

  日期：1994.6

  The first total synthesis of the highly unstable biological mediator 12-ketoeicosatetraenoic acid (12-KETE) 3 and its 8,9-trans-isomer 20 is presented. The strategy focuses on the stable precursor dithiane 13 and its conversion to 9 and 20. Biochemical experiments show that the two isomers are not interconverted in vivo, raising the possibility that the trans-isomer 20 may be formed by a primary biochemical mechanism.
• Dehydrogenase reductase 9 (SDR9C4) and related homologs recognize a broad spectrum of lipid mediator oxylipins as substrates
  作者：Olga V. Belyaeva、Samuel E. Wirth、William E. Boeglin、Suman Karki、Kelli R. Goggans、Stacy G. Wendell、Kirill M. Popov、Alan R. Brash、Natalia Y. Kedishvili

  DOI：10.1016/j.jbc.2021.101527

  日期：2022.1
• Method and systems for creating and screening patient metabolite profile to diagnose current medical condition, diagnose current treatment state and recommend new treatment regimen
  申请人：Kurek Itzhak

  公开号：US20190214145A1

  公开（公告）日：2019-07-11

  Disclosed are methods and systems for building a database of metabolite profiles correlated with disease states and treatment regiments, then defining an individual patient's metabolite profile, and then screening the patient's profile against the database to recommend potential effective treatment regimens.
• METHODS OF IMPROVING CANCER CHEMOTHERAPY
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20200197368A1

  公开（公告）日：2020-06-25

  Provided are methods and compositions for prolonging survival and/or reducing or inhibiting tumor growth in a cancer subject receiving a regimen of one or more chemotherapeutic agents, an inhibitor of soluble epoxide hydrolase (sEHi) and a non-steroidal anti-inflammatory drug (NSAID) that inhibits one or more enzymes selected from the group consisting of cyclo-oxygenase (“COX”)-1, COX-2, and 5-lipoxygenase (“5-LOX”). The methods and compositions decrease toxicity and/or adverse side effects in subjects receiving a regimen of one or more chemotherapeutic agents.
• [EN] BIOMARKER IN BLOOD FOR MACULAR EDEMA AND USE THEREOF<br/>[FR] BIOMARQUEUR DANS LE SANG D'UN ŒDÈME MACULAIRE ET SON UTILISATION<br/>[KO] 당뇨병성 황반부종에 대한 혈액내 바이오마커 및 이의 용도
  申请人：KONKUK UNIV INDUSTRIAL COOPERATION CORPORATION

  公开号：WO2021225371A1

  公开（公告）日：2021-11-11

  본 발명은 제2형 당뇨병환자에서, 혈중 대사물질중 대조군과 비교하여 통계적으로 유의미하게 차별되는 아미노산, 유기화합물 및 옥시리핀을 선별하였다. 이중, 아스파라긴(Asparagine), 아스파르트산(Aspartic acid), 글루탐산(Glutamic acid), 시스테인(Cysteine), 리신(Lysine), 시트르산(Citric acid) 및 요산(Uric acid)과 옥시리핀인 12-옥소 ETE(12-oxo ETE), 15-옥소 ETE(15-oxo ETE), 9-옥소 ODE(9-oxo ODE) 및 20-카르복시류코트리엔 B4(20-carboxy leukotriene B4)의 컷오프 값이 AUC>0.7인 것을 확인하였다. 또한, DME 환자군과 비-DME 환자군에서 상기의 혈중 대사체가 유의미한 차이를 나타내어, DME의 정확한 진단에 이용할 수 있는 것을 확인하였다.