3β-hydroxy-5-cholenamide | 475102-50-2

• 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: 3β-hydroxy-5-cholenamide
• 英文别名: (4R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanamide
• CAS: 475102-50-2
• 化学式: C₂₄H₃₉NO₂
• 分子量: 373.579
• InChiKey: SXUGJFNHBLLZLI-QIZZZRFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3B-羟基-D5-胆烯酸 在 三乙胺 、 氯甲酸异丁酯 、 氨 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.17h， 以93%的产率得到3β-hydroxy-5-cholenamide
  参考文献：
  名称：

  Structure–activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect

  摘要：

  A number of hereditary diseases are caused by defective protein trafficking due to a folding defect resulting from point mutations in proteins. Ligands that bind to the folding intermediates of such mutant proteins and rescue their trafficking defects, known as pharmacological chaperones, have promise for the treatment of certain genetic diseases, including Fabry disease, cystic fibrosis, and Niemann-Pick disease type C. Here we show that this pharmacological chaperone effect can be used for ligand screening, that is, binding of candidate ligands can be detected by monitoring the ligand-mediated correction of a localization defect caused by artificially introduced point mutations of the protein of interest. Using this method, we discovered novel steroidal ligands of Niemann-Pick type C1-like 1 (NPC1L1), an intestinal cholesterol transporter that is the target of the cholesterol absorption inhibitor ezetimibe, and conducted structure-activity relationship studies. We also present data indicating that the binding site of the new ligands is distinct from both the N-terminal sterol-binding domain and the ezetimibe-binding site. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.022

文献信息

• [EN] POLYNUCLEOTIDES FOR DISRUPTING IMMUNE CELL ACTIVITY AND METHODS OF USE THEREOF<br/>[FR] POLYNUCLÉOTIDES SERVANT À PERTURBER L'ACTIVITÉ DE CELLULE IMMUNITAIRE ET PROCÉDÉS POUR LES UTILISER
  申请人：MODERNATX INC

  公开号：WO2020227510A1

  公开（公告）日：2020-11-12

  The disclosure features isolated polynucleotides, such as mRNAs, encoding a polypeptide that disrupts immune cell activity, such as T cell or B cell activity, including mRNAs comprising one or more modified nucleobase. The immune cell disruptor polynucleotides encode a polypeptide that comprises a first domain that mediates association of the polypeptide with an immune cell component and a second domain that mediates inhibition of immune cell activity when the polypeptide is expressed in the immune cell. The disclosure also features methods of using the same, for example, for inhibiting immune responses when administered to a subject, such as to inhibit autoimmune reactions.

  该披露涉及孤立的多聚核苷酸，如编码破坏免疫细胞活性的多聚核苷酸，例如T细胞或B细胞活性的mRNA，包括包含一个或多个修饰的核碱基的mRNA。这些免疫细胞破坏多聚核苷酸编码一个包括第一个结构域的多肽，该结构域介导多肽与免疫细胞组分的结合，以及一个介导当多肽在免疫细胞中表达时抑制免疫细胞活性的第二结构域。该披露还涉及使用相同的方法，例如，将其用于向受试者施用时抑制免疫反应，例如用于抑制自身免疫反应。
• Structure–activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect
  作者：Fumika Karaki、Kenji Ohgane、Kosuke Dodo、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2013.06.022

  日期：2013.9

  A number of hereditary diseases are caused by defective protein trafficking due to a folding defect resulting from point mutations in proteins. Ligands that bind to the folding intermediates of such mutant proteins and rescue their trafficking defects, known as pharmacological chaperones, have promise for the treatment of certain genetic diseases, including Fabry disease, cystic fibrosis, and Niemann-Pick disease type C. Here we show that this pharmacological chaperone effect can be used for ligand screening, that is, binding of candidate ligands can be detected by monitoring the ligand-mediated correction of a localization defect caused by artificially introduced point mutations of the protein of interest. Using this method, we discovered novel steroidal ligands of Niemann-Pick type C1-like 1 (NPC1L1), an intestinal cholesterol transporter that is the target of the cholesterol absorption inhibitor ezetimibe, and conducted structure-activity relationship studies. We also present data indicating that the binding site of the new ligands is distinct from both the N-terminal sterol-binding domain and the ezetimibe-binding site. (C) 2013 Elsevier Ltd. All rights reserved.