Losartan是一种血管紧张素II受体拮抗剂（IC50=20nM）。
Cas No.:114798-26-4
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Losartan is an angiotensin II receptor antagonist (IC50=20nM). Losartan works by selectively blocking the AT1 receptor of angiotensin II. Losartan can be used for the treatment of hypertension and diabetic nephropathy[1-4].
In vitro, pretreatment of Vero E6 cells with Losartan (1–100μM) for 1 hour, followed by infection with SARS-CoV-2 (MOI=0.01) and culture for 96 hours, Losartan significantly reduced viral nucleoprotein levels and inhibited viral replication[5]. Pretreatment of MV3 cells with Losartan (0.7μM) for 30 minutes, followed by treatment with ATII (100nM), Losartan significantly inhibited NHE1 activity in the cells[6].
In vivo, Losartan (5-50mg/kg; oral administration) was administered to Swiss mice with 5-FU-induced intestinal mucositis for 4 days. Losartan significantly prevented the 5-FU-induced intestinal mucositis effects[7]. Losartan (10mg/kg) was orally administered daily via drinking water to CD2F1 mice bearing C26 cells for 19 days. Losartan prevented tumor-induced muscle mass loss, reduced tumor weight, attenuated myocardial interleukin-6 expression, improved cardiomyocyte calcium signaling, and increased cardiomyocyte contraction speed, contractile function, and blood pressure in tumor-bearing mice[8].
References:
[1] Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814.
[2] Burnier M. Angiotensin II type 1 receptor blockers. Circulation. 2001 Feb 13;103(6):904-12.
[3] Ashry O, Schnecko A, Clauss WG, et al. Evidence for expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells. Respir Physiol Neurobiol. 2014 May 1;195:37-40.
[4] Saleh N, Cosarderelioglu C, Vajapey R, et al. Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL-10-/- Mice. J Gerontol A Biol Sci Med Sci. 2022 Sep 1;77(9):1784-1788.
[5] Nejat R, Sadr AS, Freitas B, et al. Losartan Inhibits SARS-CoV-2 Replication in Vitro. J Pharm Pharm Sci. 2021;24:390-399.
[6] Olschewski DN, Hofschröer V, Nielsen N, et al. The Angiotensin II Type 1 Receptor Antagonist Losartan Affects NHE1-Dependent Melanoma Cell Behavior. Cell Physiol Biochem. 2018;45(6):2560-2576.
[7] Oliveira MMB, de Araújo AA, Ribeiro SB, et al. Losartan improves intestinal mucositis induced by 5-fluorouracil in mice. Sci Rep. 2021 Dec 1;11(1):23241.
[8] Stevens SC, Velten M, Youtz DJ, et al. Losartan treatment attenuates tumor-induced myocardial dysfunction. J Mol Cell Cardiol. 2015 Aug;85:37-47.
Losartan是一种血管紧张素II受体拮抗剂（IC50=20nM）。Losartan可通过选择性阻断血管紧张素II的AT1受体发挥作用。Losartan可用于高血压和糖尿病肾病的相关治疗[1-4]。
在体外，Losartan（1–100μM）预处理Vero E6细胞1小时，随后以SARS-CoV-2（MOI=0.01）感染后培养96小时。Losartan显著降低病毒核蛋白水平，同时抑制病毒复制[5]。Losartan（0.7μM）预处理MV3细胞30分钟，随后以ATII（100nM）处理。Losartan可显著抑制细胞中NHE1的活性[6]。
在体内，Losartan（5-50mg/kg；口服）用于处理由5-FU诱导肠黏膜炎的Swiss小鼠，持续4天。Losartan显著预防了5-FU诱导的肠黏膜炎效应[7]。Losartan（10mg/kg）每日通过饮用水口服处理携带C26细胞的CD2F1小鼠，持续19天。Losartan预防了肿瘤诱导的肌肉质量损失，减少了肿瘤重量，减轻了心肌白细胞介素-6表达，改善了心肌细胞钙信号传导，提高了心肌细胞收缩速度、收缩功能和肿瘤小鼠的血压[8]。
| Cell experiment [1]: | |
Cell lines | Vero E6 cells (African green monkey kidney cell line) |
Preparation Method | Vero E6 cells were plated at 2 x 10⁴ cells/well in a 96-well plate and incubated overnight at 37°C. Losartan was prepared in DMEM to concentrations from 1μM to 100μM. For pre-infection treatment, cells were preincubated with Losartan for 1 hour, then infected with SARS-CoV-2 at a MOI=0.01 for 1 hour. After infection, fresh Losartan-containing media was added. For post-infection treatment, cells were first infected with SARS-CoV-2 at a MOI=0.01 for 1 hour, then Losartan-containing media was added. Cells were incubated for 96 hours at 37°C, 5% CO₂. |
Reaction Conditions | 1-100μM; pre-incubation 1 hour, incubation 96 hours. |
Applications | Losartan treatment showed a dose-dependent and significant reduction in SARS-CoV-2 replication. Pre-infection treatment reduced SARS-CoV-2 nuclear protein levels, and post-infection treatment decreased viral replication. The half-maximal effective concentration (EC₅₀) of Losartan was 13.7μM for pre-infection treatment and 41μM for post-infection treatment. |
| Animal experiment [2]: | |
Animal models | Swiss mice (Mus musculus) |
Preparation Method | Intestinal mucositis was induced by a single intraperitoneal administration of 5-fluorouracil (5-FU; 450mg/kg). Losartan or saline was orally administered 30min before 5-FU injection and daily for 4 days. On the 4th day, animals were euthanized and segments of small intestine were collected for analysis. |
Dosage form | 5, 25 or 50mg/kg; oral administration; daily for 4 days. |
Applications | Losartan prevented 5-FU-induced intestinal mucositis effects including histopathological damage (shortened villi, loss of crypt architecture, inflammatory cell infiltration), partially rescued body weight loss, prevented leukopenia, decreased pro-inflammatory cytokine levels (TNF-α and IL-1β), reduced oxidative stress markers (MDA and GSH), and modulated mRNA expression of NF-κB p65, TWEAK and Fn14. |
References: | |
| Cas No. | 114798-26-4 | SDF | |
| 别名 | 氯沙坦; DuP-753 | ||
| 化学名 | [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | ||
| Canonical SMILES | CCCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NNN=N4)CO)Cl | ||
| 分子式 | C22H23ClN6O | 分子量 | 422.91 |
| 溶解度 | ≥ 84.6mg/mL in DMSO | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3646 mL | 11.8228 mL | 23.6457 mL |
| 5 mM | 472.9 μL | 2.3646 mL | 4.7291 mL |
| 10 mM | 236.5 μL | 1.1823 mL | 2.3646 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
- View current batch:
- Purity: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet