STAT3抑制剂VII | 1041438-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: STAT3抑制剂VII
• 英文名称: ethyl 1-(4-cyano-2,3,5,6-tetrafluorophenyl)-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: STAT3 inhibitor VII；ethyl 1-(4-cyano-2,3,5,6-tetrafluorophenyl)-6,7,8-trifluoro-4-oxoquinoline-3-carboxylate
• CAS: 1041438-68-9
• 化学式: C₁₉H₇F₇N₂O₃
• 分子量: 444.265
• InChiKey: FOEBLBGFGWQSRQ-UHFFFAOYSA-N

物化性质

• 沸点：
  519.8±50.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)
• 溶解度：
  DMSO: 5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  70.4
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  STAT3抑制剂VII 在 硫酸 作用下， 以 水 为溶剂， 反应 20.0h， 生成 1-(4-cyano-2,3,5,6-tetrafluorophenyl)-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Inhibition of the Signal Transducer and Activator of Transcription-3 (STAT3) Signaling Pathway by 4-Oxo-1-Phenyl-1,4-Dihydroquinoline-3-Carboxylic Acid Esters

  摘要：

  The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylicacid ethyl ester 4 as a potential STAT3 pathway inhibitor. Optimization of this HTS hit led to the identification of the 7-cyano analogue 8, which inhibited STAT3-Y705 phosphorylation with an EC(50) Of 170 nM. Compound 8 also inhibited cytokine induced JAK activation but did not inhibit BCR-ABL activated STAT5 phosphorylation in K562 cells.

  DOI：

  10.1021/jm701271y
• 作为产物：
  描述：

  4-氨基-2,3,5,6-四氟苯甲腈 、 合成左氧氟沙星 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 2.0h， 以1.31 g的产率得到STAT3抑制剂VII
  参考文献：
  名称：

  Inhibition of the Signal Transducer and Activator of Transcription-3 (STAT3) Signaling Pathway by 4-Oxo-1-Phenyl-1,4-Dihydroquinoline-3-Carboxylic Acid Esters

  摘要：

  The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylicacid ethyl ester 4 as a potential STAT3 pathway inhibitor. Optimization of this HTS hit led to the identification of the 7-cyano analogue 8, which inhibited STAT3-Y705 phosphorylation with an EC(50) Of 170 nM. Compound 8 also inhibited cytokine induced JAK activation but did not inhibit BCR-ABL activated STAT5 phosphorylation in K562 cells.

  DOI：

  10.1021/jm701271y

文献信息

• INHIBITORS OF MITOCHONDRIAL STAT3 AND USES THEREOF IN MODULATION OF MAST CELL EXOCYTOSIS
  申请人：Yissum Research Development Company of the Hebrew University of Jerusalem Ltd

  公开号：US20160113900A1

  公开（公告）日：2016-04-28

  The invention provides composition of matter comprising at least one STAT3 inhibiting moiety or any vehicle, matrix, nano- or micro-particle comprising the same, associated with at least one mitochondrial targeting moiety. The invention further provides compositions comprising said mitochondrial-targeted STAT3 inhibitor, methods and uses thereof in inhibiting mast cell degranulation and in treating disorders induced by activation of MC.

  该发明提供了一种物质组合物，包括至少一种STAT3抑制基团或任何载体、基质、纳米或微粒，该组合物与至少一种线粒体靶向基团相关联。该发明还提供了包含所述线粒体靶向STAT3抑制剂的组合物，以及在抑制肥大细胞脱颗粒和治疗由MC激活引起的疾病中的方法和用途。
• METHODS OF INHIBITING CELL PROLIFERATION AND METTL8 ACTIVITY
  申请人：NATIONAL UNIVERSITY OF SINGAPORE

  公开号：US20200222444A1

  公开（公告）日：2020-07-16

  The disclosure provides a method of inhibiting proliferation of a cell, inhibiting m3C formation in a cell, inhibiting activity of Mettl8 in a cell, or activating ATM and p53 in a cell, the method comprising contacting the cell with a Mettl8 inhibitor. The disclosure also provides a composition comprising a cell with a reduced expression or activity of Mettl8. In another aspect, the disclosure provides methods of rendering a tumor cell sensitive to a cancer therapy.
• Inhibition of the Signal Transducer and Activator of Transcription-3 (STAT3) Signaling Pathway by 4-Oxo-1-Phenyl-1,4-Dihydroquinoline-3-Carboxylic Acid Esters
  作者：Jun Xu、Derek C. Cole、Chao-Pei Betty Chang、Ramzi Ayyad、Magda Asselin、Wenshan Hao、James Gibbons、Scott A. Jelinsky、Kathryn A. Saraf、Kaapjoo Park

  DOI：10.1021/jm701271y

  日期：2008.7.1

  The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylicacid ethyl ester 4 as a potential STAT3 pathway inhibitor. Optimization of this HTS hit led to the identification of the 7-cyano analogue 8, which inhibited STAT3-Y705 phosphorylation with an EC(50) Of 170 nM. Compound 8 also inhibited cytokine induced JAK activation but did not inhibit BCR-ABL activated STAT5 phosphorylation in K562 cells.