Ac-PLGLYAL-Dox | 360780-98-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: Ac-PLGLYAL-Dox
• 英文别名: (2S)-1-acetyl-N-[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide
• CAS: 360780-98-9
• 化学式: C₆₆H₈₈N₈O₂₀
• 分子量: 1313.47
• InChiKey: IUOZLSPXKIQNGM-YGSUAAAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  94
• 可旋转键数：
  27
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  424
• 氢给体数：
  13
• 氢受体数：
  20

反应信息

• 作为产物：
  描述：

  Ac-PLGLYAL 、 盐酸多柔比星 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 Ac-PLGLYAL-Dox
  参考文献：
  名称：

  Discovery of matrix metalloproteases selective and activated peptide–doxorubicin prodrugs as anti-tumor agents

  摘要：

  To selectively target doxorubicin (Dox) to tumor tissue and thereby improve the therapeutic index and/or efficacy of Dox, matrix metalloproteinases (MMP) activated peptide-Dox prodrugs were designed and synthesized by coupling MMP-cleavable peptides to Dox. Preferred conjugates were good substrates for MMPs, poor substrates for neprilysin, an off-target proteinase, and stable in blood ex vivo. When administered to mice with HT1080 xenografts, conjugates, such as 19, preferentially released Dox in tumor relative to heart tissue and prevented tumor growth with less marrow toxicity than Dox. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.084

文献信息

• Discovery of matrix metalloproteases selective and activated peptide–doxorubicin prodrugs as anti-tumor agents
  作者：Zilun Hu、Xiangjun Jiang、Charles F. Albright、Nilsa Graciani、Eddy Yue、Mingzhu Zhang、Shu-Yun Zhang、Robert Bruckner、Melody Diamond、Randine Dowling、Maria Rafalski、Swamy Yeleswaram、George L. Trainor、Steven P. Seitz、Wei Han

  DOI：10.1016/j.bmcl.2009.12.084

  日期：2010.2

  To selectively target doxorubicin (Dox) to tumor tissue and thereby improve the therapeutic index and/or efficacy of Dox, matrix metalloproteinases (MMP) activated peptide-Dox prodrugs were designed and synthesized by coupling MMP-cleavable peptides to Dox. Preferred conjugates were good substrates for MMPs, poor substrates for neprilysin, an off-target proteinase, and stable in blood ex vivo. When administered to mice with HT1080 xenografts, conjugates, such as 19, preferentially released Dox in tumor relative to heart tissue and prevented tumor growth with less marrow toxicity than Dox. (C) 2009 Elsevier Ltd. All rights reserved.