TG-55

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: TG-55
• 英文别名: (5Z)-5-[[3-ethoxy-4-[(2,5,7,8-tetramethyl-6-prop-2-enoxy-3,4-dihydrochromen-2-yl)methoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione
• 化学式: C₂₉H₃₃NO₆S
• 分子量: 523.65
• InChiKey: SEQJPQCNWROLIZ-IWIPYMOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  乙基香兰素 在 哌啶 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 TG-55
  参考文献：
  名称：

  Development of Small-Molecule Cyclin D1-Ablative Agents

  摘要：

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-{[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.

  DOI：

  10.1021/jm060057h

文献信息

• SMALL MOLECULE BCL-X1/BCL-2 BINDING INHIBITORS
  申请人：Chen Ching-Shih

  公开号：US20100168184A1

  公开（公告）日：2010-07-01

  Bcl-xL/Bcl-2 binding inhibitors useful in the treatment of unwanted proliferating cells, including cancers and precancers, in subjects in need of such treatment. Also provided are methods of treating a subject having unwanted proliferating cells comprising administering a therapeutically effective amount of a Bcl-xL/Bcl-2 binding inhibitor described herein to a subject in need of such treatment. Also provided are methods of preventing the proliferation of unwanted proliferating cells, such as cancers and precancers, in a subject comprising the step of administering a therapeutically effective amount of a Bcl-xL/Bcl-2 binding inhibitor described herein to a subject at risk of developing a condition characterized by unwanted proliferating cells.
• US7566787B2
  申请人：——

  公开号：US7566787B2

  公开（公告）日：2009-07-28
• US7714005B2
  申请人：——

  公开号：US7714005B2

  公开（公告）日：2010-05-11
• US8309582B2
  申请人：——

  公开号：US8309582B2

  公开（公告）日：2012-11-13
• Development of Small-Molecule Cyclin D1-Ablative Agents
  作者：Jui-Wen Huang、Chung-Wai Shiau、Jian Yang、Da-Sheng Wang、Hao-Chieh Chiu、Ching-Yu Chen、Ching-Shih Chen

  DOI：10.1021/jm060057h

  日期：2006.7.1

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.