手霉素A,从链霉菌得来 | 52665-74-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 手霉素A,从链霉菌得来
• 中文别名: 手霉素A,从链霉菌得来；手霉素A
• 英文名称: Manumycin A
• 英文别名: (2E,4E,6R)-N-[(1S,5S,6R)-5-hydroxy-5-[(1E,3E,5E)-7-[(2-hydroxy-5-oxocyclopenten-1-yl)amino]-7-oxohepta-1,3,5-trienyl]-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]-2,4,6-trimethyldeca-2,4-dienamide
• CAS: 52665-74-4
• 化学式: C₃₁H₃₈N₂O₇
• 分子量: 550.6
• InChiKey: TWWQHCKLTXDWBD-MVTGTTCWSA-N

物化性质

• 沸点：
  863.6±65.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于 DMSO（高达 10 mg/ml）、乙醇（高达 5 mg/ml）或 DMF（高达 20 mg/ml）
• 稳定性/保质期：

  如果按照规格使用和储存，则不会分解，也未有已知危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  7

制备方法与用途

生物活性

Manumycin A 是一种抗生素。作为一种选择性、竞争性的 farnesyltransferase (FTase) 抑制剂，它与 farnesylpyrophosphate (Ki = 1.2 μM) 结合，并且是非竞争性抑制剂 Ras 蛋白质的。Manumycin A 可诱导细胞凋亡并表现出抗肿瘤活性。该化合物通过靶向抑制 Ras/Raf/ERK1/2 信号转导，以及外泌体生物发生 (exosome biogenesis) 和分泌过程。

靶点

• Farnesyltransferase
• Ras
• nSMase 抑制剂

文献信息

• PARA-QUINOL DERIVATIVES AND METHODS OF STEREO SELECTIVELY SYNTHESIZING AND USING SAME
  申请人：Plourde Guy L.

  公开号：US20090318548A1

  公开（公告）日：2009-12-24

  This application relates to para-quinol derivatives, such as analogues of manumycins, aranorosins and gymnastatins. This application also relates to methods of synthesizing and using the para-quinol derivatives. In one embodiment of the invention a compound having the chemical structure (I) is provided wherein X 1 and X 2 are carbon atoms either joined by double bond or joined by a single bond and comprising constituents of an epoxide ring or a hydroxyethylene moiety; X 3 and X 4 are carbon atoms either joined by double bond or joined by a single bond and comprising constituents of an epoxide ring; R 1 is selected from the group consisting of branched alkyl chains, unbranched alkyl chains, cycloalkyl groups, aromatic groups, alcohols, ethers, amines, and substituted or unsubstituted ureas, esters, aldehydes and carboxylic acids; and R 2 is selected from the group consisting of H, OH and NHR 3 wherein R 3 is a nitrogen protecting group. In a particular embodiment of the invention R 1 is a polyunsaturated carbon chain as found in biologically active manumycins. The applicant's synthetic method may involve diasteroselective formation of a spirolactone in an oxidative spiroannulation process using tyrosine or a tyrosine derivative having a chiral centre as a starting material.

  本申请涉及对位喹啉衍生物，例如曼纽霉素、阿拉诺罗辛和体操霉素的类似物。本申请还涉及合成和使用对位喹啉衍生物的方法。在发明的一个实施例中，提供了具有化学结构（I）的化合物，其中X1和X2是由双键连接或单键连接的碳原子，并包括环氧环或羟基乙烯基的组分；X3和X4是由双键连接或单键连接的碳原子，并包括环氧环的组分；R1选自支链烷基链，直链烷基链，环烷基团，芳香族团，醇，醚，胺和取代或未取代的脲、酯、醛和羧酸；R2选自H，OH和NHR3，其中R3是氮保护基。在发明的一个特定实施例中，R1是生物活性曼纽霉素中发现的多不饱和碳链。申请人的合成方法可能涉及使用酪氨酸或手性中心的酪氨酸衍生物作为起始材料，在氧化螺环化过程中二面体选择性地形成螺内酯。
• PANEL OF BIOMARKERS FOR PREDICTION OF FTI EFFICACY
  申请人：Levitan Diane

  公开号：US20080090242A1

  公开（公告）日：2008-04-17

  The present invention provides, inter alia, methods for selecting a patient with cancer for treatment with a farnesyl protein transferase inhibitor as well as methods for treating said patient.
• METHODS AND COMPOSITIONS FOR TREATING INFLAMMATORY DISEASE OR DISORDER
  申请人：THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

  公开号：US20210123061A1

  公开（公告）日：2021-04-29

  Described herein are methods and compositions for treating inflammatory disease. Aspects of the invention relates to administering to a subject an agent that inhibits RSK1. Another aspect of the invention relates to administering the STAT1 phosphorylation.
• [EN] TREATMENT OF VIRAL INFECTION WITH PRENYLTRANSFERASE INHIBITORS<br/>[FR] TRAITEMENT D'UNE INFECTION VIRALE AVEC DES INHIBITEURS DE PRÉNYLTRANSFÉRASE
  申请人：EIGER BIOPHARMACEUTICALS INC

  公开号：WO2011088126A2

  公开（公告）日：2011-07-21

  Inhibitors of prenylation such as farnesyl transferase inhibitors can be used to treat HDV infection.