MOA-Phe-Phe-Lys(pEBA)-OH | 1187396-30-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: MOA-Phe-Phe-Lys(pEBA)-OH
• CAS: 1187396-30-0
• 化学式: C₄₅H₆₁N₅O₆
• 分子量: 768.009
• InChiKey: OOSSOKGPUXANTG-OHJMLHFGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.05
• 重原子数：
  56.0
• 可旋转键数：
  21.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  168.72
• 氢给体数：
  5.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  氯甲酸-9-芴基甲酯 、 MOA-Phe-Phe-Lys(pEBA)-OH 在 N-甲基吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Acquisition of a Potent and Selective TC-PTP Inhibitor via a Stepwise Fluorophore-Tagged Combinatorial Synthesis and Screening Strategy

  摘要：

  Protein tyrosine phosphatases (PTPs) regulate a broad range of cellular processes including proliferation, differentiation, migration, apoptosis, and immune responses. Dysfunction of PTP activity is associated with cancers, metabolic syndromes, and autoimmune disorders. Consequently, small molecule PTP inhibitors should serve not only as powerful tools to delineate the physiological roles of these enzymes in vivo but also as lead compounds for therapeutic development. We describe a novel stepwise fluorophore-tagged combinatorial library synthesis and competitive fluorescence polarization screening approach that transforms a weak and general PTP inhibitor into an extremely potent and selective TC-PTP inhibitor with highly efficacious cellular activity. The result serves as a proof-of-concept in PTP inhibitor development, as it demonstrates the feasibility of acquiring potent, yet highly selective, cell permeable PTP inhibitory agents. Given the general nature of the approach, this strategy should be applicable to other PTP. targets.

  DOI：

  10.1021/ja903733z
• 作为产物：
  描述：

  Fmoc-[4-(phosphonodifluoromethyl)phenyl]alanine 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以13.6 mg的产率得到MOA-Phe-Phe-Lys(pEBA)-OH
  参考文献：
  名称：

  Acquisition of a Potent and Selective TC-PTP Inhibitor via a Stepwise Fluorophore-Tagged Combinatorial Synthesis and Screening Strategy

  摘要：

  Protein tyrosine phosphatases (PTPs) regulate a broad range of cellular processes including proliferation, differentiation, migration, apoptosis, and immune responses. Dysfunction of PTP activity is associated with cancers, metabolic syndromes, and autoimmune disorders. Consequently, small molecule PTP inhibitors should serve not only as powerful tools to delineate the physiological roles of these enzymes in vivo but also as lead compounds for therapeutic development. We describe a novel stepwise fluorophore-tagged combinatorial library synthesis and competitive fluorescence polarization screening approach that transforms a weak and general PTP inhibitor into an extremely potent and selective TC-PTP inhibitor with highly efficacious cellular activity. The result serves as a proof-of-concept in PTP inhibitor development, as it demonstrates the feasibility of acquiring potent, yet highly selective, cell permeable PTP inhibitory agents. Given the general nature of the approach, this strategy should be applicable to other PTP. targets.

  DOI：

  10.1021/ja903733z

文献信息

• Inhibitors of protein tyrosine phosphatases
  申请人：Zhang Zhong-Yin

  公开号：US09217012B2

  公开（公告）日：2015-12-22

  Disclosed herein are compounds that selectively inhibit members of the PTP family of enzymes. Synthesized compounds demonstrated selective inhibition of TC-PTP. Also provided are methods of using the compounds and formulations containing the compounds. Also described is a fluorescence-tagged combinatorial library synthesis and screening method. And methods of using these compounds to effect enzyme activity both in cells and in vitro as well as method of using these compounds to treat diseases in human and animals.

  本文公开了一些选择性抑制PTP酶家族成员的化合物。合成的化合物表现出对TC-PTP的选择性抑制作用。还提供了使用这些化合物的方法和含有这些化合物的配方。还描述了一种荧光标记的组合库合成和筛选方法。以及使用这些化合物在细胞和体外中影响酶活性的方法，以及使用这些化合物治疗人类和动物疾病的方法。