4-((S)-3-((S)-1-(6-(benzylcarbamoyl)-4'-carbamoylbiphenyl-3-ylamino)-4-methyl-1-oxopentan-2-ylamino)-2-(4-cyanobenzamido)-3-oxopropyl)phenyl dihydrogen phosphate | 1283116-38-0

• 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: 4-((S)-3-((S)-1-(6-(benzylcarbamoyl)-4'-carbamoylbiphenyl-3-ylamino)-4-methyl-1-oxopentan-2-ylamino)-2-(4-cyanobenzamido)-3-oxopropyl)phenyl dihydrogen phosphate
• 英文别名: [4-[(2S)-3-[[(2S)-1-[4-(benzylcarbamoyl)-3-(4-carbamoylphenyl)anilino]-4-methyl-1-oxopentan-2-yl]amino]-2-[(4-cyanobenzoyl)amino]-3-oxopropyl]phenyl] dihydrogen phosphate
• CAS: 1283116-38-0
• 化学式: C₄₄H₄₃N₆O₉P
• 分子量: 830.834
• InChiKey: JMEKYOKPXWRIOH-YDAXCOIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  60
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  250
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-溴-4-硝基苯甲酸 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 草酰氯 、 tin(II) chloride dihdyrate 、 水 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.87h， 生成 4-((S)-3-((S)-1-(6-(benzylcarbamoyl)-4'-carbamoylbiphenyl-3-ylamino)-4-methyl-1-oxopentan-2-ylamino)-2-(4-cyanobenzamido)-3-oxopropyl)phenyl dihydrogen phosphate
  参考文献：
  名称：

  Design, synthesis, and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein

  摘要：

  Aberrant activation of oncogenic signal transducer and activator of transcription 3 (STAT3) protein signaling pathways has been extensively implicated in human cancers. Given STAT3's prominent dysregulatory role in malignant transformation and tumorigenesis, there has been a significant effort to discover STAT3-specific inhibitors as chemical probes for defining the aberrant STAT3-mediated molecular events that support the malignant phenotype. To identify novel, STAT3-selective inhibitors suitable for interrogating STAT3 signaling in tumor cells, we explored the design of hybrid molecules by conjugating a known STAT3 inhibitory peptidomimetic, ISS610 to the high-affinity STAT3-binding peptide motif derived from the ILR/gp-130. Several hybrid molecules were examined in in vitro biophysical and biochemical studies for inhibitory potency against STAT3. Lead inhibitor 14aa was shown to strongly bind to STAT3 (K-D = 900 nM), disrupt STAT3: phosphopeptide complexes (K-i = 5 mu M) and suppress STAT3 activity in in vitro DNA binding activity/electrophoretic mobility shift assay (EMSA). Moreover, lead STAT3 inhibitor 14aa induced a time-dependent inhibition of constitutive STAT3 activation in v-Src transformed mouse fibroblasts (NIH3T3/v-Src), with 80% suppression of constitutively-active STAT3 at 6 h following treatment of NIH3T3/v-Src. However, STAT3 activity recovered at 24 h after treatment of cells, suggesting potential degradation of the compound. Results further showed a suppression of aberrant STAT3 activity in NIH3T3/v-Src by the treatment with compound 14aa-OH, which is the non-pTyr version of compound 14aa. The effect of compounds 14aa and 14aa-OH are accompanied by a moderate loss of cell viability. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.010

文献信息

• Phosphatase Binding Compounds and Methods of Using Same
  申请人：Yale University

  公开号：US20200268897A1

  公开（公告）日：2020-08-27

  The present invention provides bifunctional compounds that efficiently dephosphorylate certain phospho-activated target proteins. Such target proteins can be any protein involved in the pathway of a disease or disorder, such as but not limited to cancer, neurodegeneration, metabolic disease, diabetes, insulin resistance, and so forth.
• Design, synthesis, and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein
  作者：Vijay M. Shahani、Peibin Yue、Steven Fletcher、Sumaiya Sharmeen、Mahadeo A. Sukhai、Diana P. Luu、Xiaolei Zhang、Hong Sun、Wei Zhao、Aaron D. Schimmer、James Turkson、Patrick T. Gunning

  DOI：10.1016/j.bmc.2010.12.010

  日期：2011.3

  Aberrant activation of oncogenic signal transducer and activator of transcription 3 (STAT3) protein signaling pathways has been extensively implicated in human cancers. Given STAT3's prominent dysregulatory role in malignant transformation and tumorigenesis, there has been a significant effort to discover STAT3-specific inhibitors as chemical probes for defining the aberrant STAT3-mediated molecular events that support the malignant phenotype. To identify novel, STAT3-selective inhibitors suitable for interrogating STAT3 signaling in tumor cells, we explored the design of hybrid molecules by conjugating a known STAT3 inhibitory peptidomimetic, ISS610 to the high-affinity STAT3-binding peptide motif derived from the ILR/gp-130. Several hybrid molecules were examined in in vitro biophysical and biochemical studies for inhibitory potency against STAT3. Lead inhibitor 14aa was shown to strongly bind to STAT3 (K-D = 900 nM), disrupt STAT3: phosphopeptide complexes (K-i = 5 mu M) and suppress STAT3 activity in in vitro DNA binding activity/electrophoretic mobility shift assay (EMSA). Moreover, lead STAT3 inhibitor 14aa induced a time-dependent inhibition of constitutive STAT3 activation in v-Src transformed mouse fibroblasts (NIH3T3/v-Src), with 80% suppression of constitutively-active STAT3 at 6 h following treatment of NIH3T3/v-Src. However, STAT3 activity recovered at 24 h after treatment of cells, suggesting potential degradation of the compound. Results further showed a suppression of aberrant STAT3 activity in NIH3T3/v-Src by the treatment with compound 14aa-OH, which is the non-pTyr version of compound 14aa. The effect of compounds 14aa and 14aa-OH are accompanied by a moderate loss of cell viability. (C) 2010 Elsevier Ltd. All rights reserved.