20-hydroxylumisterol 3 | 1307299-09-7

• 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
• 英文名称: 20-hydroxylumisterol 3
• 英文别名: US20240131036, Example 4；(3S,9R,10S,13S,14R,17S)-17-[(2S)-2-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 1307299-09-7
• 化学式: C₂₇H₄₄O₂
• 分子量: 400.645
• InChiKey: XXLNXSKHDUPHHK-MUMZUMCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  cholesta-5,7-dien-3β,20-diol 生成 20-hydroxylumisterol 3
  参考文献：
  名称：

  Lumisterol 由 CYP11A1 代谢：新途径的发现。

  摘要：

  Lumisterol3 (L3) 是在暴露于高剂量紫外线 B 辐射期间通过 7-脱氢胆固醇 (7-DHC) 的光化学转化产生的。已经假设 L3 没有生物活性，不会在体内代谢。然而，L3 的一些合成衍生物显示出生物活性。本研究的目的是测试 CYP11A1 代谢 L3 的能力。L3 与牛或人 CYP11A1 的孵育导致形成三种主要产物和许多次要产物。牛 CYP11A1 对溶解在 2-羟丙基-β-环糊精中的 L3 代谢的催化效率约为所报道的维生素 D3 和胆固醇的 20%。三种主要产物的结构经NMR鉴定为24-羟基-L3、22-羟基-L3和20,22-二羟基-L3。22-羟基-L3 被牛 CYP11A1 进一步代谢为 20,22-二羟基-L3。22-羟基-L3 和 20,22-二羟基-L3 都产生了一种从真实标准和质谱鉴定为孕酮（pL）（L3 的 C20-C22 侧链裂解产物）和两种三羟基-L3

  DOI：

  10.1016/j.biocel.2014.08.004

文献信息

• Enzymatic Production or Chemical Synthesis and Uses for 5,7-Dienes and UVB Conversion Products Thereof
  申请人：Slominski Andrej

  公开号：US20120258938A1

  公开（公告）日：2012-10-11

  Provided herein are steroidal compounds that are androsta-5,7-dienes or pregna-5,7-dienes and ultraviolet B (UVB) conversion products thereof and cholecalciferol derivatives hydroxylated at one or more of C1, C17, C20, C23, C24, C25, and C26 which includes pharmaceutical, cosmeceutical or nutraceutical compositions of the steroidal compounds as shown in Tables 1A, 2A and 3. Also provided is a method for producing hydroxylated metabolites of cholecalciferol via CYP11A1, CYP24, CYP27A1, or CYP27B1 enzyme systems where the hydroxylase has an activity to hydroxylate position C1 or C20 or other position of the sidechain of a secosteroid or its 5,7-dieneal precursor and the hydroxylated metabolites so produced. Methods are provided for inhibiting proliferation of either a normally or abnormally proliferating cell, for modifying immune activity, or for treating a condition associated with the proliferating or quiescent cell or immune cells by contacting the cell with or administering any of the compounds described herein.

  本文提供的是雄甾-5,7-二烯或孕甾-5,7-二烯及其紫外线B（UVB）转化产物和羟化在C1、C17、C20、C23、C24、C25和C26上的胆钙醇衍生物，其中包括表1A、2A和3中所示的雄甾类化合物的制药、化妆品或营养品组合物。同时，本文还提供了一种通过CYP11A1、CYP24、CYP27A1或CYP27B1酶系统产生羟化代谢产物的方法，其中羟化酶具有羟化分裂素或其5,7-二烯前体的侧链的C1或C20或其他位置的活性，以及由此产生的羟化代谢产物。本文还提供了一种通过接触或给予本文所述的任何化合物来抑制正常或异常增殖细胞的增殖，修饰免疫活性或治疗与增殖或静止细胞或免疫细胞相关的疾病的方法。
• Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof
  申请人：Slominski Andrzej

  公开号：US20110118228A1

  公开（公告）日：2011-05-19

  Provided herein are steroidal compounds that are androsta-5,7-dienes or a pregna-5,7-dienes and ultraviolet B (UVB) conversion products thereof which includes pharmaceutical compositions of the steroidal compounds as shown in Tables 1 and 2. Also provided is a method for producing hydroxylated metabolites of cholecalciferol or ergocalciferol via the P450scc (CYP11A1) or CYP27B1 enzyme systems where the hydroxylase has an activity to hydroxylate position C20 of a secosteroid or its 5,7-dieneal precursor and the hydroxylated metabolites so produced. In addition, a method for inhibiting proliferation of either a normally or abnormally proliferating cell by contacting the cell with any of the compounds described herein. A related method is provided of treating a condition associated with the proliferating cell such as a cancer, a skin disorder, a defect in cell differentiation, cosmetic, prophylaxsis, or healthy cell maintenance.

  本文提供的是雄甾-5,7-二烯或孕甾-5,7-二烯及其紫外线B（UVB）转化产物的类固醇化合物，其中包括所示的表1和表2的类固醇化合物的药物组成。此外，还提供了一种通过P450scc（CYP11A1）或CYP27B1酶系统产生维生素D3或维生素D2的羟化代谢产物的方法，其中羟化酶具有羟化一个类固醇的C20位置或其5,7-二烯前体的活性，以及所产生的羟化代谢产物。此外，还提供了一种通过接触任何本文所述的化合物来抑制正常或异常增殖细胞增殖的方法。还提供了一种相关的方法，用于治疗与增殖细胞相关的疾病，例如癌症，皮肤疾病，细胞分化缺陷，美容，预防或维持健康的细胞。
• Chemical synthesis of 20S-hydroxyvitamin D3, which shows antiproliferative activity
  作者：Wei Li、Jianjun Chen、Zorica Janjetovic、Tae-Kang Kim、Trevor Sweatman、Yan Lu、Jordan Zjawiony、Robert C. Tuckey、Duane Miller、Andrzej Slominski

  DOI：10.1016/j.steroids.2010.05.021

  日期：2010.12

  20S-hydroxyvitamin D3 (20S-(OH)D3), an in vitro product of vitamin D3 metabolism by the cytochrome P450scc, was recently isolated, identified and shown to possess antiproliferative activity without inducing hypercalcemia. The enzymatic production of 20S-(OH)D3 is tedious, expensive, and cannot meet the requirements for extensive chemical and biological studies. Here we report for the first time the chemical synthesis of 20S-(OH)D3 which exhibited biological properties characteristic of the P450scc-generated compound. Specifically, it was hydroxylated to 20,23-dihydroxyvitamin D3 and 17,20-dihydroxyvitamin D3 by P450scc and was converted to 1 alpha,20-dihydroxyvitamin 03 by CYP27B1. It inhibited proliferation of human epidermal keratinocytes with lower potency than 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in normal epidermal human keratinocytes, but with equal potency in immortalized HaCaT keratinocytes. It also stimulated VDR gene expression with similar potency to 1,25(OH)2D3, and stimulated involucrin (a marker of differentiation) and CYP24 gene expression, showing a lower potency for the latter gene than 1,25(OH)2D3. Testing performed with hamster melanoma cells demonstrated a dose-dependent inhibition of cell proliferation and colony forming capabilities similar or more pronounced than those of 1,25(OH)203. Thus, we have developed a chemical method for the synthesis of 20S-(OH)D3, which will allow the preparation of a series of 20S-(OH)D3 analogs to study structure-activity relationships to further optimize this class of compound for therapeutic use. (C) 2010 Elsevier Inc. All rights reserved.
• [EN] COMPOSITIONS AND METHODS OF TREATING CONDITIONS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT D'AFFECTIONS
  申请人：UAB RES FOUND

  公开号：WO2022006446A1

  公开（公告）日：2022-01-06

  The present disclosure provides for pharmaceutical composition and methods of treating a condition using the pharmaceutical composition. The condition to be treated in a subject in need of treatment can include an infection or non-viral hyper-inflammation/immune hyperactivation condition. The infection can be a coronavirus infection, HIV infection, influenza infection, or the like, where a direct or indirect result of the infection can be respiratory distress, oxidative stress, and the like that can lead to acute respiratory distress syndrome (ARDS) and/or organ dysfunction or failure.