(E)-2-(4-fluorophenylsulfonyl)-3-(1-(3-nitrophenylsulfonyl)-1H-pyrrol-2-yl)acrylonitrile | 1313613-09-0

• 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: (E)-2-(4-fluorophenylsulfonyl)-3-(1-(3-nitrophenylsulfonyl)-1H-pyrrol-2-yl)acrylonitrile
• 英文别名: (E)-2-(4-fluorophenyl)sulfonyl-3-[1-(3-nitrophenyl)sulfonylpyrrol-2-yl]prop-2-enenitrile
• CAS: 1313613-09-0
• 化学式: C₁₉H₁₂FN₃O₆S₂
• 分子量: 461.451
• InChiKey: GUCUORSUHTZMBW-YBFXNURJSA-N

物化性质

• 溶解度：
  DMSO:46.15(最大浓度 mg/mL);100.0(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  160
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

AMZ30（ML136, CS-2122）是一种选择性的PME-1共价抑制剂，其IC50值为0.60 μM。AMZ30 可以减少活细胞中PP2A的脱甲基形式。

靶点

Target	Value
PME-1 (Cell-free assay)	0.60 μM

反应信息

• 作为产物：
  描述：

  4-氟苯磺酰基乙腈 在 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (E)-2-(4-fluorophenylsulfonyl)-3-(1-(3-nitrophenylsulfonyl)-1H-pyrrol-2-yl)acrylonitrile
  参考文献：
  名称：

  Discovery and Optimization of Sulfonyl Acrylonitriles as Selective, Covalent Inhibitors of Protein Phosphatase Methylesterase-1

  摘要：

  The serine hydrolase protein phosphatase methylesterase-1 (PME-1) regulates the methylesterification state of protein phosphatase 2A (PP2A) and has been implicated in cancer and Alzheimer's disease. We recently reported a fluorescence polarization-activity-based protein profiling (fluopol-ABPP) high-throughput screen for PME-1 that uncovered a remarkably potent and selective class of aza-beta-lactam (ABL) PME-1 inhibitors. Here, we describe a distinct set of sulfonyl acrylonitrile inhibitors that also emerged from this screen. The optimized compound, 28 (AMZ30), selectively inactivates PME-1 and reduces the demethylated form of PP2A in living cells. Considering that 28 is structurally unrelated to ABL inhibitors of PME-1, these agents, together, provide a valuable set of pharmacological probes to study the role of methylation in regulating PP2A function. We furthermore observed that several serine hydrolases were sensitive to analogues of 28, suggesting that more extensive structural exploration of the sulfonyl acrylonitrile chemotype may result in useful inhibitors for other members of this large enzyme class.

  DOI：

  10.1021/jm200502u

文献信息

• PME-1 as a biomarker to predict and diagnose an increased risk of endometrial cancer and gene silencing of PME-1 to inhibit epithelial to mesenchymal transition
  申请人：Medical Diagnostic Laboratories, L.L.C.

  公开号：US10167472B2

  公开（公告）日：2019-01-01

  Disclosed are methods of attenuating activity of the PME-1 gene. siRNAs or shRNAs are used to target against PME-1, thereby reducing the PME-1 mRNA. It is disclosed that the siRNAs or shRNAs targeted against PME-1 attenuate the epithelial to mesenchymal transition, thereby inhibit endometrial cancer development. A kit containing siRNA or shRNA reagents for attenuating the PME-1 gene expression is also disclosed.

  公开了减弱 PME-1 基因活性的方法。使用 siRNAs 或 shRNAs 靶向 PME-1，从而减少 PME-1 mRNA。据公开，针对 PME-1 的 siRNAs 或 shRNAs 可减轻上皮向间充质的转化，从而抑制子宫内膜癌的发展。还公开了一种含有 siRNA 或 shRNA 试剂的试剂盒，用于减弱 PME-1 基因的表达。
• PME-1 AS A BIOMARKER TO PREDICT AND DIAGNOSE AN INCREASED RISK OF ENDOMETRIAL CANCER AND GENE SILENCING OF PME-1 TO INHIBIT EPITHELIAL TO MESENCHYMAL TRANSITION
  申请人：Rice Lyndi

  公开号：US20140323546A1

  公开（公告）日：2014-10-30

  Disclosed are methods of attenuating activity of the PME-1 gene. siRNAs or shRNAs are used to target against PME-1, thereby reducing the PME-1 mRNA. It is disclosed that the siRNAs or shRNAs targeted against PME-1 attenuate the epithelial to mesenchymal transition, thereby inhibit endometrial cancer development. A kit containing siRNA or shRNA reagents for attenuating the PME-1 gene expression is also disclosed.
• PME-1 AS A BIOMARKER TO PREDICT AND DIAGNOSE ENDOMETRIAL AND BREAST CANCER AND GENE SILENCING OF PME-1 TO INHIBIT EPITHELIAL TO MESENCHYMAL TRANSITION
  申请人：Rice Lyndi M.

  公开号：US20150284723A1

  公开（公告）日：2015-10-08

  Disclosed are methods of attenuating activity of the PME-1 gene. siRNAs or shRNAs are used to target against PME-1, thereby reducing the PME-1 mRNA. It is disclosed that the siRNAs or shRNAs targeted against PME-1 attenuate the epithelial to mesenchymal transition, thereby inhibit endometrial cancer and triple negative breast cancer development. A kit containing siRNA or shRNA reagents for attenuating the PME-1 gene expression is also disclosed.
• US9657349B2
  申请人：——

  公开号：US9657349B2

  公开（公告）日：2017-05-23
• US9663789B2
  申请人：——

  公开号：US9663789B2

  公开（公告）日：2017-05-30