GLPBio

Losartan

Catalog No.: GC10249Purity:>98.50%
COASDSData Sheet
Losartan is an angiotensin II receptor antagonist (IC50=20nM).

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Losartan
Cas No.: 114798-26-4
10mM (in 1mL DMSO)In Stock
$35.00
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500mgIn Stock
$28.00
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1gIn Stock
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5gIn Stock
$84.00
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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.

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.

Product Documents

Purity:>98.50%Appearance:A solid
COASDSData Sheet

Chemical Properties

CAS No.
114798-26-4
Chemical Name
[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
Molecular Formula
C22H23ClN6O
Molecular Weight
422.91
Solubility
≥ 84.6mg/mL in DMSO
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

Reviews

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