SH-4-54

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: SH-4-54
• 英文别名: 4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-methylphenylsulfonamido)acetamido)benzoic acid；4-(N-(4-cyclohexylbenzyl)-2-((2,3,4,5,6-pentafluoro-N-methylphenyl)sulfonamido)acetamido)benzoic acid；4-[(4-cyclohexylphenyl)methyl-[2-[methyl-(2,3,4,5,6-pentafluorophenyl)sulfonylamino]acetyl]amino]benzoic acid
• 化学式: C₂₉H₂₇F₅N₂O₅S
• 分子量: 610.602
• InChiKey: VFPYGNNOSJWBHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.98
• 重原子数：
  42.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  94.99
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  SH-4-54 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma

  摘要：

  The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (K-D = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.

  DOI：

  10.1021/ml4003138
• 作为产物：
  描述：

  2,3,4,5,6-五氟苯磺酰氯 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 、 三苯基二氯化膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 4.41h， 生成 SH-4-54
  参考文献：
  名称：

  Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma

  摘要：

  The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (K-D = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.

  DOI：

  10.1021/ml4003138

文献信息

• [EN] METHODS OF TARGETING APE1/REF-1 TO INHIBIT HYPOXIA SIGNALING GENES<br/>[FR] PROCÉDÉS DE CIBLAGE D'APE1/REF -1 POUR INHIBER LES GÈNES DE SIGNALISATION DE L'HYPOXIE
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2016186853A1

  公开（公告）日：2016-11-24

  Methods for targeting apurinic/apyrimidinic endonuclease1/redox effector factor 1 (APEl/Ref-1) are disclosed. More particularly, methods for inhibiting APEl/Ref-1 and hypoxia-mediated signaling for decreasing survival and invasion of tumor cells exposed to hypoxic conditions are disclosed.

  本发明揭示了用于靶向apurinic / apyrimidinic内切酶1 / 氧化还原效应因子1（APEl / Ref-1）的方法。更具体地，揭示了用于抑制APEl / Ref-1和缺氧介导的信号传导的方法，以减少暴露于缺氧条件下的肿瘤细胞的生存和侵袭。
• SALICYCLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF
  申请人：The Governing Council of the University of Toronto

  公开号：US20150158894A1

  公开（公告）日：2015-06-11

  The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

  本发明涉及新型化合物、含有该化合物的组合物以及使用该化合物抑制STAT3和/或STAT5活性或治疗STAT3或STAT5依赖性癌症的方法；或其药学上可接受的盐、溶剂或前药。
• Salicylic acid derivatives, pharmaceutically acceptable salt thereof, composition thereof and method of use thereof
  申请人：The Governing Council of the University of Toronto

  公开号：US10377780B2

  公开（公告）日：2019-08-13

  The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

  本发明涉及抑制 STAT3 和/或 STAT5 活性或使用上述化合物治疗 STAT3 或 STAT5 依赖性癌症的新型化合物、含有上述化合物的组合物和方法； 或其药学上可接受的盐、溶液或原药。
• Methods of targeting APE/Ref-1 to inhibit hypoxia signaling genes
  申请人：Indiana University Research and Technology Corporation

  公开号：US10772859B2

  公开（公告）日：2020-09-15

  Methods for targeting apurinic/apyrimidinic endonuclease1/redox effector factor 1 (APE1/Ref-1) are disclosed. More particularly, methods for inhibiting APE1/Ref-1 and hypoxia-mediated signaling for decreasing survival and invasion of tumor cells exposed to hypoxic conditions are disclosed.

  本研究公开了靶向嘌呤/嘧啶内切酶1/氧化还原效应因子1（APE1/Ref-1）的方法。更具体地说，公开了抑制 APE1/Ref-1 和缺氧介导的信号转导以降低暴露于缺氧条件下的肿瘤细胞的存活率和侵袭性的方法。
• [EN] NEW SALICYLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS D'ACIDE SALICYLIQUE, SEL DE QUALITÉ PHARMACEUTIQUE CORRESPONDANT, COMPOSITION ET PROCÉDÉ D'UTILISATION CORRESPONDANTS
  申请人：UNIV TORONTO

  公开号：WO2013177534A3

  公开（公告）日：2015-05-28