Losartan

Catalog No.S5067

Losartan Chemical Structure

Molecular Weight(MW): 422.91

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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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]

+ Expand
  • 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
  • Formulation: drinking water
  • 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

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03435939 Not yet recruiting Cystic Fibrosis University of Kansas Medical Center March 10 2019 Early Phase 1
NCT03435939 Not yet recruiting Cystic Fibrosis University of Kansas Medical Center March 10 2019 Early Phase 1
NCT03692013 Not yet recruiting HypertensionNephropathy Fifth Affiliated Hospital Sun Yat-Sen University|Third Affiliated Hospital Sun Yat-Sen University December 1 2018 Phase 4
NCT03692013 Not yet recruiting HypertensionNephropathy Fifth Affiliated Hospital Sun Yat-Sen University|Third Affiliated Hospital Sun Yat-Sen University December 1 2018 Phase 4
NCT03632213 Recruiting Mucopolysaccharidosis IV A|Mucopolysaccharidosis VI|Mucopolysaccharidoses|MPS IV A|MPS VI|MPS - Mucopolysaccharidosis|Morquio A Syndrome|Morquio Syndrome A|Morquio Syndrome Hospital de Clinicas de Porto Alegre|The Isaac Foundation November 7 2018 Phase 2
NCT03603938 Not yet recruiting Chronic Kidney Disease Patients Fifth Affiliated Hospital Sun Yat-Sen University November 1 2018 Not Applicable

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID