全-反式-18-羟基维甲酸 | 63531-93-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 全-反式-18-羟基维甲酸
• 英文名称: (2E,4E,6E,8E)-3,7-dimethyl-9-<6,6-dimethyl-2-(hydroxymethyl)-1-cyclohexen-1-yl>-2,4,6,8-nonatetraenoic acid
• 英文别名: 18-Hydroxyretinoic acid；all-trans-18-Hydroxyretinoic acid；(2E,4E,6E,8E)-9-[2-(hydroxymethyl)-6,6-dimethylcyclohexen-1-yl]-3,7-dimethylnona-2,4,6,8-tetraenoic acid
• CAS: 63531-93-1
• 化学式: C₂₀H₂₈O₃
• 分子量: 316.441
• InChiKey: XSJOIRFEYHJNAW-FCKHSPHMSA-N

物化性质

• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

18-羟基视黄酸是维甲酸的人类已知代谢物。

18-Hydroxyretinoic acid is a known human metabolite of Tretinoin.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  2-甲基环己酮 在 吡啶 、 氢氧化钾 、 lithium aluminium tetrahydride 、 正丁基锂 、 硫酸 、 sodium methylate 、 potassium carbonate 、 对甲苯磺酸 、 potassium amide 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 36.68h， 生成 全-反式-18-羟基维甲酸
  参考文献：
  名称：

  Retinoic acid metabolites. 3. Total synthesis of (2E,4E,6E,8E)-3,7-dimethyl-9-[6,6-dimethyl-2-(hydroxymethyl)-1-cyclohexen-1-yl]-2,4,6,8-nonatetraenoic acid

  摘要：

  DOI：

  10.1021/jo00348a043

文献信息

• CYP26C1 Is a Hydroxylase of Multiple Active Retinoids and Interacts with Cellular Retinoic Acid Binding Proteins
  作者：Guo Zhong、David Ortiz、Alex Zelter、Abhinav Nath、Nina Isoherranen

  DOI：10.1124/mol.117.111039

  日期：2018.5

  The clearance of retinoic acid (RA) and its metabolites is believed to be regulated by the CYP26 enzymes, but the specific roles of CYP26A1, CYP26B1, and CYP26C1 in clearing active vitamin A metabolites have not been defined. The goal of this study was to establish the substrate specificity of CYP26C1, and determine whether CYP26C1 interacts with cellular retinoic acid binding proteins (CRABPs). CYP26C1 was found to effectively metabolize all- trans retinoic acid ( at RA), 9- cis -retinoic acid (9- cis -RA), 13- cis -retinoic acid, and 4-oxo- at RA with the highest intrinsic clearance toward 9- cis -RA. In comparison with CYP26A1 and CYP26B1, CYP26C1 resulted in a different metabolite profile for retinoids, suggesting differences in the active-site structure of CYP26C1 compared with other CYP26s. Homology modeling of CYP26C1 suggested that this is attributable to the distinct binding orientation of retinoids within the CYP26C1 active site. In comparison with other CYP26 family members, CYP26C1 was up to 10-fold more efficient in clearing 4-oxo- at RA (intrinsic clearance 153 μ l/min/pmol) than CYP26A1 and CYP26B1, suggesting that CYP26C1 may be important in clearing this active retinoid. In support of this, CRABPs delivered 4-oxo- at RA and at RA for metabolism by CYP26C1. Despite the tight binding of 4-oxo- at RA and at RA with CRABPs, the apparent Michaelis-Menten constant in biological matrix ( K m) value of these substrates with CYP26C1 was not increased when the substrates were bound with CRABPs, in contrast to what is predicted by free drug hypothesis. Together these findings suggest that CYP26C1 is a 4-oxo- at RA hydroxylase and may be important in regulating the concentrations of this active retinoid in human tissues.

  视黄酸（RA）及其代谢物的清除被认为是由CYP26酶调控的，但CYP26A1、CYP26B1和CYP26C1在清除活性维生素A代谢物中的具体作用尚未明确。本研究的目标是建立CYP26C1的底物特异性，并确定CYP26C1是否与细胞视黄酸结合蛋白（CRABPs）相互作用。研究发现，CYP26C1能够有效地代谢全反式视黄酸（at RA）、9-顺式视黄酸（9-cis-RA）、13-顺式视黄酸和4-氧-全反式视黄酸，其中对9-cis-RA的内源性清除率最高。与CYP26A1和CYP26B1相比，CYP26C1对视黄醇类化合物展现出不同的代谢物谱，提示CYP26C1的活性位点结构与其他CYP26酶存在差异。CYP26C1的同源建模表明，这与视黄醇在CYP26C1活性位点内的不同结合取向有关。与其他CYP26家族成员相比，CYP26C1在清除4-氧-全反式视黄酸方面的效率高达CYP26A1和CYP26B1的10倍（内源性清除率为153 μl/min/pmol），这表明CYP26C1在清除这一活性视黄醇方面可能具有重要意义。支持这一点的是，CRABPs将4-氧-全反式视黄酸和全反式视黄酸输送给CYP26C1进行代谢。尽管4-氧-全反式视黄酸和全反式视黄酸与CRABPs结合紧密，但在生物基质中这些底物与CYP26C1的表观米氏常数（K m）在底物与CRABPs结合时并未增加，这与自由药物假说的预测相反。这些发现共同表明，CYP26C1是一种4-氧-全反式视黄酸羟化酶，可能在调节人类组织中这一活性视黄醇的浓度方面具有重要作用。
• Stem cell-like cells
  申请人：Fornix Biosciences N.V.

  公开号：EP1176189A1

  公开（公告）日：2002-01-30

  The invention relates to the field of embryology, embryogenesis, molecular genetics, (veterinary) medicine and zoo-technical sciences, and to the generation of stem cell-like cells. The invention provides a method for obtaining a stem cell-like cell from a sample taken from a multicellular organism, preferably an organism with some measure of differentiated tissue, thus preferably being beyond the morula stage, comprising culturing cells from said sample and allowing for transcription, translation or expression by at least one of said cells of a gene or gene product that in general is differentially expressed at the various different phases of embryonic development of the organism as described above.

  本发明涉及胚胎学、胚胎发生、分子遗传学、（兽医）医学和动物技术科学领域，以及干细胞样细胞的产生。本发明提供了一种从多细胞生物体样本中获得类干细胞的方法，该样本最好是具有一定分化组织的生物体，因此最好是超过蜕膜期的生物体，包括培养所述样本中的细胞，并允许所述细胞中的至少一个转录、翻译或表达基因或基因产物，如上所述，该基因或基因产物一般在生物体胚胎发育的各个不同阶段有不同的表达。
• Oxidized forms of retinoic acid as ligands for peroxisome proliferator activated receptor gamma
  申请人：The Brigham and Women's Hospital, Inc.

  公开号：US20020031539A1

  公开（公告）日：2002-03-14

  The present invention is directed to certain oxidized forms of retinoic acid and their precursors that have been found to be effective in treating conditions that respond to agents that bind to and activate the human peroxisome proliferator activated receptor-gamma. Specific compounds include oxidized all-trans retinoic acid; oxidized 9-cis retinoic acid; and reduced 4-oxo-retinoic acid. The compounds may be used in treating a number of diseases or conditions including diabetes, low body weight, atherosclerosis, and certain forms of cancer.

  本发明涉及某些氧化型维甲酸及其前体，已发现这些氧化型维甲酸及其前体可有效治疗对与人过氧化物酶体增殖物激活受体-γ结合并激活受体-γ的药剂有反应的病症。具体化合物包括氧化全反式维甲酸、氧化 9-顺式维甲酸和还原 4-氧代维甲酸。这些化合物可用于治疗多种疾病或病症，包括糖尿病、低体重、动脉粥样硬化和某些形式的癌症。
• STEM CELL-LIKE CELLS
  申请人：Fornix Biosciences N.V.

  公开号：EP1301590A2

  公开（公告）日：2003-04-16
• USE OF RETINOIC ACID IN T-CELL MANUFACTURING
  申请人：Immatics US, Inc.

  公开号：US20200318068A1

  公开（公告）日：2020-10-08

  The present disclosure generally relates to methods of improving T cell homing to organs or tissues by utilizing compounds and compositions, for example, retinoic acid receptor agonists. In an aspect, the disclosure provides for organ-homing engineered T cells for treating diseases, associated compositions, and methods for preparing thereof.