cyclo-Leu-N-Me-Val-D-Leu-D-Phe-3,3-diphenyl-D-Ala | 1610523-48-2

• 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: cyclo-Leu-N-Me-Val-D-Leu-D-Phe-3,3-diphenyl-D-Ala
• 英文别名: SM258；cyclo[D-Dip-D-Phe-D-Leu-N(Me)Val-Leu]；(3R,6R,9R,12S,15S)-9-benzhydryl-6-benzyl-1-methyl-3,12-bis(2-methylpropyl)-15-propan-2-yl-1,4,7,10,13-pentazacyclopentadecane-2,5,8,11,14-pentone
• CAS: 1610523-48-2
• 化学式: C₄₂H₅₅N₅O₅
• 分子量: 709.929
• InChiKey: NWXOKFAPRAEQBX-JFLIOZJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  52
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  HO-Leu-N-Me-Val-D-Leu-D-Phe-3,3-diphenyl-D-Ala-NH₂ 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 二氯甲烷 为溶剂， 以39%的产率得到cyclo-Leu-N-Me-Val-D-Leu-D-Phe-3,3-diphenyl-D-Ala
  参考文献：
  名称：

  Chemically Accessible Hsp90 Inhibitor That Does Not Induce a Heat Shock Response

  摘要：

  Recent cancer therapies have focused on targeting biology networks through a single regulatory protein. Heat shock protein 90 (hsp90) is an ideal oncogenic target as it regulates over 400 client proteins and cochaperones. However, clinical inhibitors of hsp90 have had limited success; the primary reason being that they induce a heat shock response. We describe the synthesis and biological evaluation of a new hsp90 inhibitor, SM253. The previous generation on which SM253 is based (SM145) has poor overall synthetic yields, low solubility, and micromolar cytotoxicity. By comparison SM253 has relatively high overall yields, good aqueous solubility, and is more cytotoxic than its parent compound. Verification that hsp90 is SM253's target was accomplished using pull-down and protein folding assays. SM253 is superior to both SM145 and the clinical candidate 17-AAG as it decreases proteins related to the heat shock response by 2-fold, versus a 2-4-fold increase observed when cells are treated with 17-AAG.

  DOI：

  10.1021/ml500114p

文献信息

• Chemically Accessible Hsp90 Inhibitor That Does Not Induce a Heat Shock Response
  作者：Yen Chin Koay、Jeanette R. McConnell、Yao Wang、Seong Jong Kim、Laura K. Buckton、Flora Mansour、Shelli R. McAlpine

  DOI：10.1021/ml500114p

  日期：2014.7.10

  Recent cancer therapies have focused on targeting biology networks through a single regulatory protein. Heat shock protein 90 (hsp90) is an ideal oncogenic target as it regulates over 400 client proteins and cochaperones. However, clinical inhibitors of hsp90 have had limited success; the primary reason being that they induce a heat shock response. We describe the synthesis and biological evaluation of a new hsp90 inhibitor, SM253. The previous generation on which SM253 is based (SM145) has poor overall synthetic yields, low solubility, and micromolar cytotoxicity. By comparison SM253 has relatively high overall yields, good aqueous solubility, and is more cytotoxic than its parent compound. Verification that hsp90 is SM253's target was accomplished using pull-down and protein folding assays. SM253 is superior to both SM145 and the clinical candidate 17-AAG as it decreases proteins related to the heat shock response by 2-fold, versus a 2-4-fold increase observed when cells are treated with 17-AAG.