| 1225383-32-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• CAS: 1225383-32-3
• 化学式: C₂₅H₃₂N₂O₅
• 分子量: 440.539
• InChiKey: YSTISTKQKZZODJ-PJCIUIFUSA-N

物化性质

• 沸点：
  637.3±65.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  32.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  108.98
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  、 (S)-N-{2-[2-(2-aminoethoxy)ethoxy]ethyl}-4-methyl-2-(4-phenylbutanamido)pentanamide hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以62%的产率得到(2E,4E,6E,8E)-2-cyanoethyl 3,7-dimethyl-9-((E)-2,6,6-trimethyl-3-{2-[2-(2-{2-[(S)-4-methyl-2-(4-phenylbutanamido)pentanamido]ethoxy}ethoxy)ethylamino]-2-oxoethoxyimino}cyclohex-1-enyl)nona-2,4,6,8-tetraenoate
  参考文献：
  名称：

  Development of target protein-selective degradation inducer for protein knockdown

  摘要：

  Our previous technique for inducing selective degradation of target proteins with ester-type SNIPER (Specific and Nongenetic Inhibitor-of-apoptosis-proteins (IAPs)-dependent Protein ERaser) degrades both the target proteins and IAPs. Here, we designed a small-molecular amide-type SNIPER to overcome this issue. As proof of concept, we synthesized and biologically evaluated an amide-type SNIPER which induces selective degradation of cellular retinoic acid binding protein II (CRABP-II), but not IAPs. Such small-molecular, amide-type SNIPERs that induce target protein-selective degradation without affecting IAPs should be effective tools to study the biological roles of target proteins in living cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.057

文献信息

• Double protein knockdown of cIAP1 and CRABP-II using a hybrid molecule consisting of ATRA and IAPs antagonist
  作者：Yukihiro Itoh、Minoru Ishikawa、Risa Kitaguchi、Keiichiro Okuhira、Mikihiko Naito、Yuichi Hashimoto

  DOI：10.1016/j.bmcl.2012.04.134

  日期：2012.7

  Protein knockdown can be achieved by the use of a small molecule that possesses affinity for both the target protein and ubiquitin ligase. We have designed such a degradation-inducing molecule targeting cIAP1 and CRABP-II, which are involved in proliferation of several cancer cell lines and in neuroblastoma growth, respectively. As a CRABP-II-recognizing moiety, all-trans retinoic acid ( ATRA, 3), a physiological ligand of CRABP, was chosen. As a cIAP1-recognizing moiety, MV1 ( 5), which is a cIAP1/cIAP2/XIAP panligand, was chosen. Although cIAP1 itself possesses ubiquitin ligase activity, we expected that its decomposition would be efficiently mediated by related molecules, including cIAP2 and XIAP, which also possess ubiquitin ligase activity. The designed degradation inducer 6, in which ATRA ( 3) and MV1 ( 5) moieties are connected via a linker, was synthesized and confirmed to induce efficient degradation of both cIAP1 and CRABP-II. It showed potently inhibited the proliferation of IMR32 cells. (C) 2012 Elsevier Ltd. All rights reserved.