GLPBio

Losartan

Catalog No.: GC10249Purity:>98.50%
COASDSData Sheet
LosartÁn es un antagonista de los receptores de la angiotensina II, que compite con la uniÓn de la angiotensina II a los receptores AT1 con IC50 de 20 nM.

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Losartan
Cas No.: 114798-26-4
10mM (in 1mL DMSO)In Stock
$35.00
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500mgIn Stock
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1gIn Stock
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5gIn Stock
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    610, 366–372 (2022)
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    187(9):2288-2304 (2024)
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    183(7):1867-1883 (2020)
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Descripción (Description)

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.

Protocolo (Protocol)

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:
[1] Nejat R, Sadr AS, Freitas B, et al. Losartan Inhibits SARS-CoV-2 Replication in Vitro. J Pharm Pharm Sci. 2021;24:390-399.
[2] 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.

Documentos del producto (Product Documents)

Purity:>98.50%Appearance:A solid
COASDSData Sheet

Propiedades químicas (Chemical Properties)

N.º CAS
114798-26-4
Nombre químico
[2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol
SMILES
CCCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NNN=N4)CO)Cl
Fórmula molecular
C22H23ClN6O
Peso molecular
422.91
Solubilidad
≥ 84.6mg/mL in DMSO
Almacenamiento
Store at -20°C
Consejos generales
Seleccione un disolvente adecuado según los datos de solubilidad del producto. Una vez preparada, divida la solución madre en alícuotas para evitar ciclos repetidos de congelación y descongelación.
Utilice las soluciones madre en un plazo de 6 meses si se conservan a -80°C, o de 1 mes si se conservan a -20°C.
Para mejorar la solubilidad, caliente el tubo a 37°C y soníquelo durante un periodo adecuado.
Condiciones de envío
Las muestras de evaluación se envían con acumuladores de frío. Los demás tamaños se envían a temperatura ambiente o, previa solicitud, con acumuladores de frío.

Calculadoras (Calculators)Molaridad / Dilución / Peso molecular / Conversión de unidades / Formulación in vivo / Solubilidad

g/mol

Reviews

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