6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-N-[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]hexanamide | 1401539-59-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: 6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-N-[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]hexanamide
• CAS: 1401539-59-0
• 化学式: C₄₃H₅₄N₄O₁₄S
• 分子量: 882.986
• InChiKey: VXJQPWWYOFTBRP-IBUXXMJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  62
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  305
• 氢给体数：
  9
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  盐酸多柔比星 、 生物素化-epsilon-氨基己酸-N-羟基丁二酰亚胺活化酯 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 16.0h， 以98%的产率得到6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-N-[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]hexanamide
  参考文献：
  名称：

  The antitumor agent doxorubicin binds to Fanconi anemia group F protein

  摘要：

  Doxorubicin, a commonly used cancer chemotherapy agent, elicits several potent biological effects, including synergistic-antitumor activity in combination with cisplatin. However, the mechanism of this synergism remains obscure. Here, we employed an improved T7 phage display screening method to identify Fanconi anemia group F protein (FANCF) as a doxorubicin-binding protein. The FANCF-doxorubicin interaction was confirmed by pull-down assay and SPR analysis. FANCF is a component of the Fanconi anemia complex, which monoubiquitinates D2 protein of Fanconi anemia group as a cellular response against DNA cross-linkers such as cisplatin. We observed that the monoubiquitination was inhibited by doxorubicin treatment. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.015

文献信息

• The antitumor agent doxorubicin binds to Fanconi anemia group F protein
  作者：Tomoe Kusayanagi、Senko Tsukuda、Satomi Shimura、Daisuke Manita、Kanako Iwakiri、Shinji Kamisuki、Yoichi Takakusagi、Toshifumi Takeuchi、Kouji Kuramochi、Atsuo Nakazaki、Kengo Sakaguchi、Susumu Kobayashi、Fumio Sugawara

  DOI：10.1016/j.bmc.2012.09.015

  日期：2012.11

  Doxorubicin, a commonly used cancer chemotherapy agent, elicits several potent biological effects, including synergistic-antitumor activity in combination with cisplatin. However, the mechanism of this synergism remains obscure. Here, we employed an improved T7 phage display screening method to identify Fanconi anemia group F protein (FANCF) as a doxorubicin-binding protein. The FANCF-doxorubicin interaction was confirmed by pull-down assay and SPR analysis. FANCF is a component of the Fanconi anemia complex, which monoubiquitinates D2 protein of Fanconi anemia group as a cellular response against DNA cross-linkers such as cisplatin. We observed that the monoubiquitination was inhibited by doxorubicin treatment. (C) 2012 Elsevier Ltd. All rights reserved.