(2E,4E)-2,4,6-Trimethyl-deca-2,4-dienoic acid {5-hydroxy-5-[(1E,3E,5E)-6-(2-hydroxy-5-oxo-cyclopent-1-enylcarbamoyl)-hexa-1,3,5-trienyl]-2-oxo-7-oxa-bicyclo[4.1.0]hept-3-en-3-yl}-amide | 52665-74-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2E,4E)-2,4,6-Trimethyl-deca-2,4-dienoic acid {5-hydroxy-5-[(1E,3E,5E)-6-(2-hydroxy-5-oxo-cyclopent-1-enylcarbamoyl)-hexa-1,3,5-trienyl]-2-oxo-7-oxa-bicyclo[4.1.0]hept-3-en-3-yl}-amide
• 英文别名: (2E,4E)-N-[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: 550.652
• InChiKey: TWWQHCKLTXDWBD-SEMJNZETSA-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）

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

反应信息

• 作为反应物：
  描述：

  (2E,4E)-2,4,6-Trimethyl-deca-2,4-dienoic acid {5-hydroxy-5-[(1E,3E,5E)-6-(2-hydroxy-5-oxo-cyclopent-1-enylcarbamoyl)-hexa-1,3,5-trienyl]-2-oxo-7-oxa-bicyclo[4.1.0]hept-3-en-3-yl}-amide 以32%的产率得到
  参考文献：
  名称：

  ZEECK, AXEL;SCHRODER, KARSTEN;FROBEL, KLAUS;GROTE, RALPH;THIERICKE, RALF, J. ANTIBIOTICS, 40,(1987) N 11, 1530-1540

  摘要：

  DOI：

文献信息

• Manumycin
  作者：Karsten Schröder、Axel Zeeck

  DOI：10.1016/s0040-4039(01)87631-0

  日期：1973.1
• ZEECK, AXEL;SCHRODER, KARSTEN;FROBEL, KLAUS;GROTE, RALPH;THIERICKE, RALF, J. ANTIBIOTICS, 40,(1987) N 11, 1530-1540
  作者：ZEECK, AXEL、SCHRODER, KARSTEN、FROBEL, KLAUS、GROTE, RALPH、THIERICKE, RALF

  DOI：——

  日期：——
• ZEECK, AXEL;FROBEL, KLAUS;HEUSEL, CHRISTA;SCHRODER, KARSTEN;THIERICKE, RA+, J. ANTIBIOTICS, 40,(1987) N 11, 1541-1548
  作者：ZEECK, AXEL、FROBEL, KLAUS、HEUSEL, CHRISTA、SCHRODER, KARSTEN、THIERICKE, RA+

  DOI：——

  日期：——
• [EN] SMALL MOLECULES THAT REDUCE FUNGAL GROWTH<br/>[FR] PETITES MOLECULES LIMITANT LA CROISSANCE FONGIQUE
  申请人：GE UNIVERSITY OF VERMONT AND S

  公开号：WO2006081327A2

  公开（公告）日：2006-08-03

  [EN] The present invention relates to methods for reducing the growth of a fungus with an anti-fungal small molecule. Methods for reducing fungal cell growth in a subject with an anti-fungal small molecule and related compositions are provided. Topical lotion formulations of an anti-fungal small molecule and a topical carrier are also provided.
  [FR] La présente invention concerne des procédés pour limiter la croissance d'un champignon au moyen d'une petite molécule antifongique. L'invention a également pour objet des procédés pour limiter la croissance de cellules fongiques chez un individu au moyen d'une petite molécule antifongique, et des compositions associées. L'invention concerne aussi des formulations de lotions topiques d'une petite molécule antifongique et d'un excipient topique.
• [EN] METHODS OF TREATMENT OF CANCER ASSOCIATED WITH CENTROSOME AMPLIFICATION<br/>[FR] MÉTHODES DE TRAITEMENT DU CANCER ASSOCIÉ À UNE AMPLIFICATION DE CENTROSOMES
  申请人：INST DE MEDICINA MOLECULAR

  公开号：WO2020130863A1

  公开（公告）日：2020-06-25

  This invention relates to the finding that centrosome amplification (CA) renders cancer cells more sensitive to certain anti-cancer compounds. The invention provides methods of treating cancer that displays centrosome amplification (CA) by administering a CA selective agent. Also provided are methods of screening for a CA selective agent comprising determining the effect of a test compound on the expression of a panel of CA associated genes in the cell and methods of determining the sensitivity of a cancer cell to a CA selective agent comprising determining the expression of a panel of CA associated genes in the cancer cell. Other aspects of the invention relate to measuring the expression of a panel of CA associated genes in order to assess a cancer condition in an individual or to assess genomic instability in a cancer cell.