(+)-3-oxo-5α-cholan-24-oic acid | 19038-19-8

• 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: (+)-3-oxo-5α-cholan-24-oic acid
• 英文别名: 3-oxo-5α-cholanoic acid-(24)；3-Oxo-5α-cholansaeure-(24)；3-Oxo-5alpha-cholan-24-oic Acid；(4R)-4-[(5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3-oxo-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 19038-19-8
• 化学式: C₂₄H₃₈O₃
• 分子量: 374.564
• InChiKey: KIQFUORWRVZTHT-LZQMWTLUSA-N

物化性质

• 熔点：
  187 °C
• 沸点：
  509.3±23.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-3-oxo-5α-cholan-24-oic acid 在 氢溴酸 、 溶剂黄146 、 铂 作用下， 生成 (3alpha,5alpha)-3-羟基胆烷-24-酸
  参考文献：
  名称：

  Berliner; Schoenheimer, Journal of Biological Chemistry, 1938, vol. 124, p. 525,535

  摘要：

  DOI：
• 作为产物：
  描述：

  (3b,5a)-3-羟基-胆烷-24-酸 在 potassium phosphate 、 rabbit aldose reductase-like protein AKR₁B₁₉ 、 烟酰胺腺嘌呤双核苷酸磷酸盐 作用下， 以 甲醇 为溶剂， 生成 (+)-3-oxo-5α-cholan-24-oic acid
  参考文献：
  名称：

  Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity

  摘要：

  In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)(1) 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and alpha-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5 alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3 beta-hydroxysteroids, showing K-m of 1.3-9.1 mu M and k(cat) of 1.1-7.6 min(-1). The stereospecific reduction was also observed in the metabolism of 5 alpha- and 5 beta-dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3 beta-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2012.07.012

文献信息

• Bile acids serve as endogenous antagonists of the Leukemia inhibitory factor (LIF) receptor in oncogenesis
  作者：Cristina Di Giorgio、Elva Morretta、Antonio Lupia、Rachele Bellini、Carmen Massa、Ginevra Urbani、Martina Bordoni、Silvia Marchianò、Ginevra Lachi、Pasquale Rapacciuolo、Claudia Finamore、Valentina Sepe、Maria Chiara Monti、Federica Moraca、Nicola Natalizi、Luigina Graziosi、Eleonora Distrutti、Michele Biagioli、Bruno Catalanotti、Annibale Donini、Angela Zampella、Stefano Fiorucci

  DOI：10.1016/j.bcp.2024.116134

  日期：2024.5

  metabolism and the intestinal microbiota. Here we demonstrated that bile acids serve as endogenous antagonist to LIFR in oncogenesis. The tissue characterization of bile acids content in non-cancer and cancer biopsy pairs from gastric adenocarcinomas (GC) demonstrated that bile acids accumulate within cancer tissues, with glyco-deoxycholic acid (GDCA) functioning as negative regulator of LIFR expression.

  白血病抑制因子 （LIF） 是白细胞介素 （IL）-6 细胞因子家族的成员，参与免疫调节、形态发生和肿瘤发生。在癌组织中，LIF 结合由 LIFRβ 亚基和糖蛋白 （gp） 形成的异二聚体受体 （LIFR）130，促进上皮间充质转化和细胞生长。胆汁酸是在宿主代谢和肠道微生物群界面处产生的胆固醇代谢物。在这里，我们证明了胆汁酸在肿瘤发生中是 LIFR 的内源性拮抗剂。胃腺癌 （GC） 非癌和癌症活检对中胆汁酸含量的组织表征表明，胆汁酸在癌组织内积累，其中糖脱氧胆酸 （GDCA） 作为 LIFR 表达的负调节因子。在来自 GC 患者的患者来源类器官 （hPDO） 中，GDCA 可逆转 LIF 诱导的干性和增殖。总之，我们已经确定次级胆汁酸是 LIFR 的第一个内源性拮抗剂，支持在 LIF 介导的肿瘤发生中开发基于胆汁酸的疗法。
• Wieland; Dane; Martius, Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1933, vol. 215, p. 15,22
  作者：Wieland、Dane、Martius

  DOI：——

  日期：——
• USE OF SQUALAMINE FOR THE MANUFACTURE OF A MEDICAMENT FOR INHIBITING NHE
  申请人：MAGAININ PHARMACEUTICALS INC.

  公开号：EP0831837A1

  公开（公告）日：1998-04-01
• [EN] USE OF SQUALAMINE FOR THE MANUFACTURE OF A MEDICAMENT FOR INHIBITING NHE<br/>[FR] UTILISATION DE SQUALAMINE DANS LA PRODUCTION D'UN MEDICAMENT INHIBANT LE NHE
  申请人：MAGAININ PHARMACEUTICALS INC.

  公开号：WO1996040151A1

  公开（公告）日：1996-12-19

  (EN) Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.(FR) L'invention concerne des composés d'aminostérols utiles en tant qu'inhibiteurs de l'échangeur sodium/proton (NHE). L'invention concerne également des modes d'utilisation de ces composés d'aminostérol, y compris ceux utilisant des composés constituant des inhibiteurs d'un spectre des NHE, ainsi que ceux utilisant des composés constituant des inhibiteurs uniquement d'un NHE spécifique. L'invention concerne en outre des technique de criblage ainsi que des dosages d'évaluation avantageux de l'activité thérapeutique d'un composé.
• Kuwada; Joyama, Yakugaku Zasshi, 1935, vol. 55, p. 978,984; dtsch. Ref. S. 183
  作者：Kuwada、Joyama

  DOI：——

  日期：——