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
* <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.)

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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. Losartan Carboxylic Acid 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

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[2]. 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[3].
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[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

    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.
Animal Study:

[4]
  • Animal Models

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

  • Dosages

    10 mg/kg/day

  • Administration

    oral

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.