ELN441958
目录号 : GC16820
ELN441958是一种强效、竞争性且选择性的bradykinin B1受体拮抗剂，Ki值为0.26nM。
Cas No.:913064-47-8
Sample solution is provided at 25 µL, 10mM.
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ELN441958 is a potent, competitive, and selective bradykinin B1 receptor antagonist with a Ki value of 0.26nM [1]. ELN441958 can target Nsp12_ortho and Nsp12_Palm1 sites and has potential inhibitory activity against SARS-CoV-2 replication[2]. ELN441958 has been widely used to alleviate thermal hyperalgesia in animal models[3].
In vitro, ELN441958 treatment at 1µM for 4h significantly inhibited octapeptide [des-Arg9]-Bradykinin (DABK) (0.1µM; 4h)-induced PTGS2 expression in human amniotic fibroblasts (HAFs)[4].
In vivo, ELN441958 treatment via subcutaneous injection at a single dose of 1mg/kg for 30min reduced anxiety-like behavior in DBA/2NCrl mice[5].
References:
[1] Hawkinson J E, Szoke B G, Garofalo A W, et al. Pharmacological, pharmacokinetic, and primate analgesic efficacy profile of the novel bradykinin B1 Receptor antagonist ELN441958[J]. The Journal of pharmacology and experimental therapeutics, 2007, 322(2): 619-630.
[2] Gervasoni S, Manelfi C, Adobati S, et al. Target prediction by multiple virtual screenings: analyzing the SARS-CoV-2 phenotypic screening by the docking simulations submitted to the MEDIATE initiative[J]. International Journal of Molecular Sciences, 2023, 25(1): 450.
[3] Wisniewski P, Gangnus T, Burckhardt B B. Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system[J]. Journal of translational medicine, 2024, 22(1): 388.
[4] Ni X, Wang W, Liu Y, et al. The bradykinin system contributes to the regulation of prostaglandin-endoperoxide synthase 2 expression in human amnion fibroblasts: Implications for term and preterm birth[J]. Frontiers in Endocrinology, 2022, 13: 873727.
[5] Rouhiainen A, Kulesskaya N, Mennesson M, et al. The bradykinin system in stress and anxiety in humans and mice[J]. Scientific reports, 2019, 9(1): 19437.
ELN441958是一种强效、竞争性且选择性的bradykinin B1受体拮抗剂，Ki值为0.26nM[1]。ELN441958可靶向Nsp12_ortho和Nsp12_Palm1位点，具有潜在的抑制SARS-CoV-2复制活性[2]。ELN441958已广泛用于缓解动物模型中的热痛觉过敏[3]。
在体外，使用1µM的ELN441958处理4小时，显著抑制了八肽[des-Arg9]-Bradykinin（DABK）（0.1µM；4h）诱导的人羊膜成纤维细胞（HAFs）中PTGS2的表达[4]。
在体内，以单剂量1mg/kg皮下注射ELN441958 30分钟，可减轻 DBA/2NCrl 小鼠的焦虑样行为[5]。
| Cell experiment [1]: | |
Cell lines | Human amnion fibroblasts (HAFs) |
Preparation Method | HAFs were cultured in DMEM medium containing 10% fetal bovine serum (FCS) and 1% antibiotics at 37°C in 5% CO2-95% air for 3 days. The medium was replaced with DMEM medium without phenol red and fetal bovine serum, and HAFs were treated with DABK (0.1µM) in the presence or absence of the ELN441958 (1µM) for 4h before measuring PTGS2 mRNA and protein abundance. |
Reaction Conditions | 1μM; 4h |
Applications | ELN441958 treatment inhibited the levels of PTGS2 mRNA and protein in HAFs induced by DABK. |
| Animal experiment [2]: | |
Animal models | DBA/2NCrl mice |
Preparation Method | 5-to 8-week-old DBA/2NCrl male mice were acclimated in a controlled temperature (22±2°C) and humidity (50±15%) facility with a 12-h light/dark cycle (lights on from 06:00 to 18:00), with ad libitum access to food and water, and housed individually for at least 1 week before experiments. Behavioral tests were performed 30 minutes after subcutaneous injection of a single dose (1mg/kg) of ELN441958. |
Dosage form | 1mg/kg for once; s.c. |
Applications | ELN441958 treatment significantly reduced anxiety-like behaviors in DBA/2NCrl mice. |
References: | |
| Cas No. | 913064-47-8 | SDF | |
| 化学名 | 7-chloro-2-(3-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carbonyl)phenyl)isoindolin-1-one | ||
| Canonical SMILES | ClC1=CC=CC(CN2C3=CC=CC(C(N4CCC5(CC4)CCN(C6=CC=NC=C6)CC5)=O)=C3)=C1C2=O | ||
| 分子式 | C29H29ClN4O2 | 分子量 | 501.02 |
| 溶解度 | DMSO : 100 mg/mL (199.59 mM) | 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 | 1.9959 mL | 9.9796 mL | 19.9593 mL |
| 5 mM | 399.2 μL | 1.9959 mL | 3.9919 mL |
| 10 mM | 199.6 μL | 998 μL | 1.9959 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。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet