pantothenate-7-amino-4-methylcoumarin | 1224691-12-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: pantothenate-7-amino-4-methylcoumarin
• 英文别名: pantothenate-7-amino-4-methylcoumarine；pAMC；(2R)-2,4-dihydroxy-3,3-dimethyl-N-[3-[(4-methyl-2-oxochromen-7-yl)amino]-3-oxopropyl]butanamide
• CAS: 1224691-12-6
• 化学式: C₁₉H₂₄N₂O₆
• 分子量: 376.409
• InChiKey: QMSSTHIQHBHLMP-KRWDZBQOSA-N

物化性质

• 沸点：
  748.4±60.0 °C(Predicted)
• 密度：
  1.320±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  pantothenate-7-amino-4-methylcoumarin 在 His/Flag-tagged human vanin-1 、 水 、 1,4-二巯基-2,3-丁二醇 、 bovine serum albumin 作用下， 反应 1.0h， 生成 7-氨基-4-甲基香豆素 、 D-泛酸
  参考文献：
  名称：

  A fluorescent assay suitable for inhibitor screening and vanin tissue quantification

  摘要：

  Vanin-1 is a pantetheinase that catalyzes the hydrolysis of pantetheine to produce pantothenic acid (vitamin B5) and cysteamine. Reported here is a highly sensitive fluorescent assay using a novel fluorescently labeled pantothenate derivative. The assay has been used for characterization of a soluble version of human vanin-1 recombinant protein, identification and characterization of hits from high-throughput screening (HTS), and quantification of vanin pantothenase activity in cell lines and tissues. Under optimized assay conditions, we quantified vanin pantothenase activity in tissue lysate and found low activity in lung and liver but high activity in kidney. We demonstrated that the purified recombinant vanin-1 consisting of the extracellular portion without the glycosylphosphatidylinositol (GPI) linker was highly active with an apparent K-m of 28 mu M for pantothenate-7-amino-4-methylcoumarin (pantothenate-AMC), which was converted to pantothenic acid and AMC based on liquid chromatography-mass spectrometry (LC-MS) analysis. The assay also performed well in a 384-well microplate format under initial rate conditions (10% conversion) with a signal-to-background ratio (S/B) of 7 and a Z factor of 0.75. Preliminary screening of a library of 1280 pharmaceutically active compounds identified inhibitors with novel chemical scaffolds. This assay will be a powerful tool for target validation and drug lead identification and characterization. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.ab.2009.12.010
• 作为产物：
  描述：

  H-beta-丙氨酰-7-氨基-4-甲基香豆素三氟乙酸盐 、 D-(-)-泛酰内酯 以 乙醇 为溶剂， 反应 48.0h， 以32 mg的产率得到pantothenate-7-amino-4-methylcoumarin
  参考文献：
  名称：

  A fluorescent assay suitable for inhibitor screening and vanin tissue quantification

  摘要：

  Vanin-1 is a pantetheinase that catalyzes the hydrolysis of pantetheine to produce pantothenic acid (vitamin B5) and cysteamine. Reported here is a highly sensitive fluorescent assay using a novel fluorescently labeled pantothenate derivative. The assay has been used for characterization of a soluble version of human vanin-1 recombinant protein, identification and characterization of hits from high-throughput screening (HTS), and quantification of vanin pantothenase activity in cell lines and tissues. Under optimized assay conditions, we quantified vanin pantothenase activity in tissue lysate and found low activity in lung and liver but high activity in kidney. We demonstrated that the purified recombinant vanin-1 consisting of the extracellular portion without the glycosylphosphatidylinositol (GPI) linker was highly active with an apparent K-m of 28 mu M for pantothenate-7-amino-4-methylcoumarin (pantothenate-AMC), which was converted to pantothenic acid and AMC based on liquid chromatography-mass spectrometry (LC-MS) analysis. The assay also performed well in a 384-well microplate format under initial rate conditions (10% conversion) with a signal-to-background ratio (S/B) of 7 and a Z factor of 0.75. Preliminary screening of a library of 1280 pharmaceutically active compounds identified inhibitors with novel chemical scaffolds. This assay will be a powerful tool for target validation and drug lead identification and characterization. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.ab.2009.12.010

文献信息

• A fluorescent assay suitable for inhibitor screening and vanin tissue quantification
  作者：Benfang H. Ruan、Derek C. Cole、Paul Wu、Amira Quazi、Karen Page、Jill F. Wright、Nelson Huang、Joseph R. Stock、Karl Nocka、Ann Aulabaugh、Rustem Krykbaev、Lori J. Fitz、Neil M. Wolfman、Margaret L. Fleming

  DOI：10.1016/j.ab.2009.12.010

  日期：2010.4

  Vanin-1 is a pantetheinase that catalyzes the hydrolysis of pantetheine to produce pantothenic acid (vitamin B5) and cysteamine. Reported here is a highly sensitive fluorescent assay using a novel fluorescently labeled pantothenate derivative. The assay has been used for characterization of a soluble version of human vanin-1 recombinant protein, identification and characterization of hits from high-throughput screening (HTS), and quantification of vanin pantothenase activity in cell lines and tissues. Under optimized assay conditions, we quantified vanin pantothenase activity in tissue lysate and found low activity in lung and liver but high activity in kidney. We demonstrated that the purified recombinant vanin-1 consisting of the extracellular portion without the glycosylphosphatidylinositol (GPI) linker was highly active with an apparent K-m of 28 mu M for pantothenate-7-amino-4-methylcoumarin (pantothenate-AMC), which was converted to pantothenic acid and AMC based on liquid chromatography-mass spectrometry (LC-MS) analysis. The assay also performed well in a 384-well microplate format under initial rate conditions (10% conversion) with a signal-to-background ratio (S/B) of 7 and a Z factor of 0.75. Preliminary screening of a library of 1280 pharmaceutically active compounds identified inhibitors with novel chemical scaffolds. This assay will be a powerful tool for target validation and drug lead identification and characterization. (C) 2009 Elsevier Inc. All rights reserved.