Losartan Carboxylic Acid (EXP-3174)

Catalog No.S5980 Batch:S598001

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Technical Data

Formula

C22H21ClN6O2
Molecular Weight 436.89 CAS No. 124750-92-1
Solubility (25°C)* In vitro DMSO 87 mg/mL (199.13 mM)
Ethanol 87 mg/mL (199.13 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Losartan Carboxylic Acid (E-3174, EXP-3174), an active carboxylic acid metabolite of Losartan, is a non-peptide angiotensin II (AT1) receptor antagonist. This compound inhibits the specific binding of [125I]-angiotensin II to VSMC with IC50 of 1.1 nM.
Targets
binding of [125I]-angiotensin II to VSMC [1]
(Cell-free assay)
1.1 nM
In vitro

Losartan Carboxylic Acid (EXP-3174) competes in vitro with the binding of angiotensin II to AT1 receptors, with an IC50 of 20 nmol/L[2]. It increases AMPK phosphorylation in a time- and dose-dependent manner in VSMCs, as well as ACC phosphorylation—a major downstream target protein in the AMPK signaling cascade—and LKB1 phosphorylation, an upstream kinase of AMPK. This compound also elevates p53 and p21 expression in a time-dependent manner, while p27 levels remain unchanged. It suppresses Ang II-induced Rb phosphorylation, along with cyclin D and cyclin E expression, which are essential for cell cycle progression. The mechanism of growth suppression by losartan involves G0/G1 cell cycle arrest, reversible through AMPK inhibition (e.g., compound C or AMPK siRNA), but not via apoptosis[3].
In vivo

Losartan has a major active metabolite, EXP 3174. Administered intravenously, this compound is 10 to 20 times more potent than losartan and has a longer duration of action. 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[2]. Treatment with losartan ameliorates the loss in the number and function of endothelial progenitor cells (EPCs) in hypertensive rats[4].

Protocol (from reference)

Cell Assay:

[3]
  • Cell lines

    VSMCs

  • Concentrations

    0, 1, 5, 10 μM

  • Incubation Time

    48 h

  • Method

    In the presence or absence of indicated concentrations of Losartan Carboxylic Acid (EXP-3174), cells were treated with Ang II or 15% FBS for 48 hrs. Cell proliferation was determined by the MTT assay.
Animal Study:

[4]
  • Animal Models

    12-week-old male Wistar-Kyoto (WKY) rats and SHR-SP

  • Dosages

    10 mg/kg/day

  • Administration

    oral

References

  • https://pubmed.ncbi.nlm.nih.gov/8385175/
  • https://pubmed.ncbi.nlm.nih.gov/11171802/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997415/
  • https://pubmed.ncbi.nlm.nih.gov/18250561/

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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