Methyl N-({(2s,3s)-3-[(Propylamino)carbonyl]oxiran-2-Yl}carbonyl)-L-Isoleucyl-L-Prolinate | 147859-80-1

• 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: Methyl N-({(2s,3s)-3-[(Propylamino)carbonyl]oxiran-2-Yl}carbonyl)-L-Isoleucyl-L-Prolinate
• 英文别名: methyl (2S)-1-[(2S,3S)-3-methyl-2-[[(2S,3S)-3-(propylcarbamoyl)oxirane-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carboxylate
• CAS: 147859-80-1
• 化学式: C₁₉H₃₁N₃O₆
• 分子量: 397.5
• InChiKey: XGWSRLSPWIEMLQ-YTFOTSKYSA-N

物化性质

• 熔点：
  153-155°C
• 沸点：
  666.3±55.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

CA-074 methyl ester (CA-074 Me, Cathepsin B Inhibitor IV) 是一种可透过膜的衍生物，属于不可逆的 cathepsin B 抑制剂。

靶点

Target	Value
Cathepsin B

体外研究

CA-074 Me 在 HL-60 细胞和布氏锥虫的血液形式中抑制 cathepsin L，但在缺少硫醇的情况下不发挥作用。在细胞内酯酶的作用下，CA-074 Me 转变为 CA-074，在 GSH-depleted 的 HL60 细胞中抑制 cathepsin B。在活细胞中，CA-074 选择性地而非 CA-074 Me 抑制 cathepsin B。在处理过的成肌细胞中，观察到肌管大小、数目和诱导的融合相关的肌酸磷酸激酶活性以及肌凝蛋白重链蛋白质均减少，并且这种效果与浓度相关；微摩尔浓度的 CA-074 Me 在处于分化的成肌细胞中可抑制 catB 活性。

体内研究

对 London APP 小鼠进行 CA074Me 给药，能够显著改善其记忆缺陷、减少脑内淀粉样斑块负荷、降低 Aβ40 和 Aβ42 的水平，并且降低来自 APP 的 CTFβ。然而，在 Swedish/London APP 小鼠中却没有这种效果。正常豚鼠的脑室内注射 CA074Me 会导致其脑内 Aβ 大量减少并抑制 β 分泌酶活性。

文献信息

• Compositions and methods for use of a protease inhibitor and adenosine for preventing organ ischemia and reperfusion injury
  申请人：Vinten-Johansen Jakob

  公开号：US20060205671A1

  公开（公告）日：2006-09-14

  Methods and compositions including combined use of a serine protease inhibitor and adenosine when administered as a single pharmaceutical composition, concomitantly or sequentially in any order to a living subject for preventing organ ischemia or reperfusion injury. The methods and compositions disclosed herein can be used in such procedures as cardiac surgery, non-surgical cardiac revascularization, organ transplantation, perfusion, ischemia, reperfusion, ischemia-reperfusion injury, oxidant injury, cytokine induced injury, shock induced injury, resuscitations injury or apoptosis.
• Method For Prophylaxis or Treatment of Feline Infectious Peritonitis
  申请人：Whittaker Gary R.

  公开号：US20110142797A1

  公开（公告）日：2011-06-16

  Provided is a method for treatment and/or prophylaxis of FIP in cats. The method is performed by administering to a cat a composition comprising a therapeutic and/or prophylactic amount of a cysteine protease inhibitor. The cysteine protease inhibitor can be a selective cathepsin B inhibitor. Also provided is a method for inhibiting FIPV replication. The method comprises contacting a cell infected with FIPV with a cysteine protease inhibitor in an amount effective to inhibit replication of FIPV. It is expected the method will be effective for therapy or prophylaxis of FIP in any species of cat and will be effective against any strain of feline coronavirus.
• PROTEIN DEGRADATION INDUCING TAG AND USAGE THEREOF
  申请人：Tokyo University of Science Foundation

  公开号：US20180164289A1

  公开（公告）日：2018-06-14

  Provided are: a protein degradation inducing tag which is a molecule that has affinity with proteases and does not inhibit degradation of a protein by proteases; a protein degradation inducing molecule that is a conjugate of at least one protein degradation inducing tag and at least one protein binding molecule that binds to a protein; and a usage of those.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• US9044486B2
  申请人：——

  公开号：US9044486B2

  公开（公告）日：2015-06-02