20S,23S-dihydroxyvitamin D₃ | 1033416-82-8

• 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: 20S,23S-dihydroxyvitamin D₃
• 英文别名: 20,23-dihydroxyvitamin D₃；20S,23-dihydroxyvitamin D3；20,23-dihydroxyvitamin D3；(20S,23)-dihydroxyvitamin D3；(2S)-2-[(1S,3aS,4E,7aS)-4-[(2Z)-2-[(5S)-5-hydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-6-methylheptane-2,4-diol
• CAS: 1033416-82-8
• 化学式: C₂₇H₄₄O₃
• 分子量: 416.645
• InChiKey: PFGAVEWICNHWDW-OZCLJXQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  20S,23S-dihydroxyvitamin D₃ 、 氢(+1)阳离子 、 氧气 、 [2Fe-2S]¹⁺ 生成 (20S,23,24)-trihydroxyvitamin D3 、 水 、 [2Fe-2S]²⁺
  参考文献：
  名称：

  Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1

  摘要：

  CYP11A1 hydroxylates vitamin 03 producing 20S-hydroxyvitamin 03 [20(OH)D3] and 20S,23-dihydroxyvitamin D3 [20,23(OH)(2)D3] as the major and most characterized metabolites. Both display immuno-regulatory and anti-cancer properties while being non-calcemic. A previous study indicated 20 (OH)D3 can be metabolized by rat CYP24A1 to products including 205,24-dihydroxyvitamin 03 [20,24 (OH)(2)D3] and 20S,25-dihydroxyvitamin 03, with both producing greater inhibition of melanoma colony formation than 20(OH)D3. The aim of this study was to characterize the ability of rat and human CYP24A1 to metabolize 20(OH)D3 and 20,23(OH)(2)D3. Both isoforms metabolized 20(OH)D3 to the same dihydroxyvitamin D species with no secondary metabolites being observed. Hydroxylation at C24 produced both enantiomers of 20,24(OH)(2)D3. For rat CYP24A1 the preferred initial site of hydroxylation was at C24 whereas the human enzyme preferred C25. 20,23(OH)(2)D3 was initially metabolized to 20S,23,24-trihydroxyvitamin D3 and 20.5,23,25-trihydroxyvitamin D3 by rat and human CYP24A1 as determined by NMR, with both isoforms showing a preference for initial hydroxylation at C25. CYP24A1 was able to further oxidize these metabolites in a series of reactions which included the cleavage of C23-C24 bond, as indicated by high resolution mass spectrometry of the products, analogous to the catabolism of 1,25(OH)(2)D3 via the C24-oxidation pathway. Similar catalytic efficiencies were observed for the metabolism of 20(OH)D3 and 20,23(OH)(2)D3 by human CYP24A1 and were lower than for the metabolism of 1,25(OH)(2)D3. We conclude that rat and human CYP24A1 metabolizes 20(OH) 03 producing only dihydroxyvitamin D3 species as products which retain biological activity, whereas 20,23(OH)(2)D3 undergoes multiple oxidations which include cleavage of the side chain. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.jsbmb.2015.02.010
• 作为产物：
  描述：

  维生素 D3 在 bovine CYP₁₁A₁ 作用下， 生成 20S-Hydroxyvitamin D3 、 20S,23S-dihydroxyvitamin D₃
  参考文献：
  名称：

  Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1

  摘要：

  CYP11A1 hydroxylates vitamin 03 producing 20S-hydroxyvitamin 03 [20(OH)D3] and 20S,23-dihydroxyvitamin D3 [20,23(OH)(2)D3] as the major and most characterized metabolites. Both display immuno-regulatory and anti-cancer properties while being non-calcemic. A previous study indicated 20 (OH)D3 can be metabolized by rat CYP24A1 to products including 205,24-dihydroxyvitamin 03 [20,24 (OH)(2)D3] and 20S,25-dihydroxyvitamin 03, with both producing greater inhibition of melanoma colony formation than 20(OH)D3. The aim of this study was to characterize the ability of rat and human CYP24A1 to metabolize 20(OH)D3 and 20,23(OH)(2)D3. Both isoforms metabolized 20(OH)D3 to the same dihydroxyvitamin D species with no secondary metabolites being observed. Hydroxylation at C24 produced both enantiomers of 20,24(OH)(2)D3. For rat CYP24A1 the preferred initial site of hydroxylation was at C24 whereas the human enzyme preferred C25. 20,23(OH)(2)D3 was initially metabolized to 20S,23,24-trihydroxyvitamin D3 and 20.5,23,25-trihydroxyvitamin D3 by rat and human CYP24A1 as determined by NMR, with both isoforms showing a preference for initial hydroxylation at C25. CYP24A1 was able to further oxidize these metabolites in a series of reactions which included the cleavage of C23-C24 bond, as indicated by high resolution mass spectrometry of the products, analogous to the catabolism of 1,25(OH)(2)D3 via the C24-oxidation pathway. Similar catalytic efficiencies were observed for the metabolism of 20(OH)D3 and 20,23(OH)(2)D3 by human CYP24A1 and were lower than for the metabolism of 1,25(OH)(2)D3. We conclude that rat and human CYP24A1 metabolizes 20(OH) 03 producing only dihydroxyvitamin D3 species as products which retain biological activity, whereas 20,23(OH)(2)D3 undergoes multiple oxidations which include cleavage of the side chain. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.jsbmb.2015.02.010

文献信息

• Hydroxylation of CYP11A1-Derived Products of Vitamin D3 Metabolism by Human and Mouse CYP27B1
  作者：Edith K. Y. Tang、Jianjun Chen、Zorica Janjetovic、Elaine W. Tieu、Andrzej T. Slominski、Wei Li、Robert C. Tuckey

  DOI：10.1124/dmd.113.050955

  日期：2013.5

  CYP27B1 than 25-hydroxyvitamin D3. CYP27B1 action on these new dihydroxy derivatives was confirmed to be 1α-hydroxylation by mass spectrometry and nuclear magnetic resonance analyses. Both 1,20,25- and 1,20,26- trihydroxyvitamin D3 were tested for their ability to inhibit melanoma (SKMEL-188) colony formation, and were significantly more active than 20(OH)D3. This study shows that CYP11A1-derived secosteroids

  CYP11A1 可以在碳 17、20、22 和 23 处羟基化维生素 D3，产生一系列具有生物活性的类固醇，它们具有抑制增殖和刺激各种细胞类型（包括癌细胞）分化的能力。由于 CYP11A1 作用的主要代谢物 20S-羟基维生素 D3 [20(OH)D3] 的 1α-羟基化对其性质有很大影响，我们检查了人和小鼠 CYP27B1 对 CYP11A1 产生的 1α-羟基化六种类固醇的能力。根据它们的 kcat/Km 值，与 25-羟基维生素 D3 相比，所有 CYP11A1 衍生的代谢物都是来自两个物种的 CYP27B1 的不良底物。没有观察到具有 17α-羟基的代谢物羟基化。17α,20-二羟基维生素 D3 可作为人 CYP27B1 的抑制剂，但对小鼠酶无效。我们还在 20 日测试了 CYP27B1 活性，24-、20,25- 和 20,26-二羟基维生素 D3，它们是 CYP24A1 或 CYP27A1
• 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。
• [EN] ENZYMATIC PRODUCTION OR CHEMICAL SYNTHESIS AND USES FOR 5,7-DIENES AND UVB CONVERSION PRODUCTS THEREOF<br/>[FR] PRODUCTION ENZYMATIQUE OU SYNTHÈSE CHIMIQUE ET UTILISATIONS POUR LES 5,7-DIÈNES ET PRODUITS DE CONVERSION UVB AINSI OBTENUS
  申请人：UNIV TENNESSEE RES FOUNDATION

  公开号：WO2009108388A2

  公开（公告）日：2009-09-03

  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. Also provided is a method for producing hydroxylated metabolites of cholecalciferol via the P450scc (CYPl IA 1) or CYP27B 1 enzyme systems 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.