AE-3763
目录号 : GC32016
AE-3763是基于多肽的人中性粒细胞弹性蛋白酶(humanneutrophilelastase)抑制剂，IC50值为29nM。
Cas No.:291778-77-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[1]D-Galactosamine shock is induced in C3H/HeN mice (6-7 w, 22-25 g). AE-3763 (10 or 100 mg/kg) is administrated intraperitoneally six times at 2 h interval. Control animals receive the vehicle (PBS) instead of AE-3763. Animal’s survival rate is observed up to 24 h after shock induction[1]. |
References: [1]. Inoue Y, et al. Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury. Bioorg Med Chem. 2009 Nov 1;17(21):7477-86. | |
AE-3763 is a peptide-based human neutrophil elastase inhibitor with an IC50 of 29 nM.
AE-3763 exhibits potent in vitro inhibitory activity against human neutrophil elastase as well as extremely high solubility and stability in water[1].
Edema and leukocytes infiltration into the lung are significantly inhibited by infusion of AE-3763. AE3763 significantly improves survival rate by 24 h in a mouse model of fatal shock associated with multiple organ dysfunction. AE-3763 dose-dependently prevents hemorrhage when given intravenously by infusion (ED50: 0.42 mg/kg/h) or by bolus injection (1.2 mg/kg). With regard to the toxicity of AE-3763 in mice, the results of a preliminary study have shown no overt toxic effect even at the high dose of 300 mg/kg, iv[1].
[1]. Inoue Y, et al. Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury. Bioorg Med Chem. 2009 Nov 1;17(21):7477-86.
| Cas No. | 291778-77-3 | SDF | |
| Canonical SMILES | O=C(O)CN1CCN(CC(N[C@H](C(N2[C@H](C(N[C@@H](C(C)C)C(C(F)(F)F)=O)=O)CCC2)=O)C(C)C)=O)C1=O | ||
| 分子式 | C23H34F3N5O7 | 分子量 | 549.54 |
| 溶解度 | DMSO : 16.67 mg/mL (30.33 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8197 mL | 9.0985 mL | 18.197 mL |
| 5 mM | 0.3639 mL | 1.8197 mL | 3.6394 mL |
| 10 mM | 0.182 mL | 0.9099 mL | 1.8197 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury
A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000 mg/ml in H(2)O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD).
Neutrophil elastase inhibitors as treatment for COPD
Chronic obstructive pulmonary disease, characterised by a slowly progressive, irreversible airways limitation, is a major worldwide cause of chronic morbidity and mortality. The imbalance between human neutrophil elastase and endogenous antiproteases may cause excess human neutrophil elastase in pulmonary tissues, which may be considered a major pathogenic factor in chronic obstructive pulmonary disease. Great effort has been devoted to finding a method to restore the balance, resulting in the discovery of potent two-typed small-molecular-weight human neutrophil elastase inhibitors. In the application of chronic obstructive pulmonary disease therapy, the human neutrophil elastase inhibitors mainly focused upon include ONO-5046, MR-889, L-694,458, CE-1037, GW-311616 and TEI-8362 as the acyl-enzyme inhibitors; and ONO-6818, AE-3763, FK-706, ICI-200,880, ZD-0892 and ZD-8321 as the transition-state inhibitors. In this review, various problems that remain to be solved in the clinical use of human neutrophil elastase inhibitors are discussed.