Losartan

For research use only.

Catalog No.S5067

13 publications

Losartan Chemical Structure

CAS No. 114798-26-4

Losartan is a selective, orally administered, nonpeptide blocker of angiotensin II type 1 (AT1) receptor used to treat high blood pressure, diabetic kidney disease, heart failure, and left ventricular enlargement.

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Selleck's Losartan has been cited by 13 publications

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Choose Selective Angiotensin Receptor Inhibitors

Biological Activity

Description Losartan is a selective, orally administered, nonpeptide blocker of angiotensin II type 1 (AT1) receptor used to treat high blood pressure, diabetic kidney disease, heart failure, and left ventricular enlargement.
Targets
AT1 receptor [1]
()
20 nM
In vitro

In vitro, losartan competes with the binding of angiotensin II to AT1 receptors; the concentration that inhibits 50% of the binding of angiotensin II (IC50) is 20 nmol/L[1]. Losartan increases AMPK phosphorylation in a time- and dose-dependent manner in VSMCs. It also increases ACC phosphorylation, a major downstream target protein in the AMPK signaling cascade, and LKB1 phosphorylation, which is an upstream kinase of AMPK. Losartan increases p53 and p21 expression in a time-dependent manner, whereas the levels of p27 are not changed. Losartan suppresses Ang II-induced Rb phosphorylation, as well as cyclin D and cyclin E expression which are required for cell cycle progression. The mechanism of growth suppression by losartan is therefore G0/G1 cell cycle arrest which is reversed by AMPK inhibition, such as compound C or AMPK siRNA, but not by apoptosis[2].

In vivo Losartan has a major active metabolite, EXP 3174. Administered intravenously, EXP3174 is 10 to 20 times more potent than losartan and has a longer duration of action than losartan. However, the oral bioavailability of EXP 3174 is very low. Losartan has a bioavailability of about 33%, the half-life averages 2 h (6-9 hours), and the rate of protein binding is 98.7% when dosed at 50-100 mg/d[1]. Treatment with losartan ameliorates the loss in the number and function of endothelial progenitor cells (EPCs) in hypertensive rats[3].

Protocol

Cell Research:

[2]

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  • Cell lines: VSMCs
  • Concentrations: 0, 1, 5, 10 μM
  • Incubation Time: 48 h
  • Method:

    Cells were treated with Ang II or 15% FBS in the presence or absence of indicated concentration of losartan for 48 hrs. Cell proliferation was determined by the MTT assay.


    (Only for Reference)
Animal Research:

[3]

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  • Animal Models: 12-week-old male Wistar-Kyoto (WKY) rats and SHR-SP
  • Dosages: 10 mg/kg/day
  • Administration: oral
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 84 mg/mL (198.62 mM)

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 422.91
Formula

C22H23ClN6O

CAS No. 114798-26-4
Storage powder
in solvent
Synonyms N/A
Smiles CCCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NNN=N4)CO)Cl

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04604756 Recruiting Drug: Losartan|Drug: Placebo Oral Tablet Healthy University of Electronic Science and Technology of China October 10 2020 Not Applicable
NCT04335123 Completed Drug: Losartan COVID-19 University of Kansas Medical Center April 4 2020 Phase 1
NCT03900793 Recruiting Drug: Losartan|Drug: Sunitinib Osteosarcoma University of Colorado Denver|National Cancer Institute (NCI) August 22 2019 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID