Azilsartan

Catalog No.S3046 Batch:S304601

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Technical Data

Formula

C25H20N4O5
Molecular Weight 456.45 CAS No. 147403-03-0
Solubility (25°C)* In vitro DMSO 91 mg/mL (199.36 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
30%PEG400 0.5%Tween80 5%propylene glycol
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Azilsartan (TAK-536) is an angiotensin II type 1 (AT1) receptor antagonist with IC50 of 2.6 nM.
Targets
AT1 receptor [1]
2.6 nM
In vitro Azilsartan inhibits the specific binding of 125I-Sar1-Ile8-AII to human angiotensin type 1 receptors. Azilsartan also inhibits the accumulation of AII-induced inositol 1-phosphate (IP1) in the cell-based assay with an IC50 value of 9.2 nM. In isolated rabbit aortic strips, Azilsartan reduces the maximal contractile response to AII with a pD'2 value of 9.9. The inhibitory effects of Azilsartan on contractile responses induced by AII persists after the strips are washed. [1] Azilsartan suppresses the increase in plasma glucose level in the oral glucose tolerance test (OGTT) without significant change in insulin concentration and improved insulin sensitivity. In skeletal muscle, Azilsartan decreases the expression of TNF-α at doses of 0.001%. In adipose tissue, Azilsartan reduces TNF-α expression but increases the expression of adiponectin, PPARγ, C/EBα, and aP2. [2] In cultured 3T3-L1 preadipocytes, Azilsartan enhances adipogenesis and exertes greater effects than valsartan on expression of genes encoding peroxisome proliferator-activated receptor-α (PPARα), PPARδ, leptin, adipsin, and adiponectin. Azilsartan also potently inhibits vascular cell proliferation in the absence of exogenously supplemented angiotensin II. [3]
In vivo In Koletsky rats, Azilsartan treatment lowers blood pressure, basal plasma insulin concentration and the homeostasis model assessment of insulin resistance index, and inhibited over-increase of plasma glucose and insulin concentrations during oral glucose tolerance test. Azilsartan downregulates 11β-hydroxysteroid dehydrogenase type 1 expression. [4]
Features A potent, orally active and specific AII receptor antagonist.

Protocol (from reference)

Kinase Assay:[1]
  • Radioligand binding studies on human AT1 receptors

    A radioligand binding assay is performed by using human AT1 receptor-coated microplates containing 4.4 to 6.2 fmol of receptors/well (10 μg of membrane protein/well). Membrane-coated wells are incubated with 45 μL of assay buffer (50 mM Tris-HCl, 5 mM MgCl2, 1 mM EDTA, and 0.005% CHAPS, pH 7.4) containing various concentrations of Azilsartan at room temperature. After 90 minutes, 5 μL of 125I-Sar1-Ile8-AII (final concentration 0.6 nM) dissolved in assay buffer is added to the wells, and the plate is incubated for 5 hours. In each step, the plate is briefly and gently shaken on a plate shaker. In washout experiments, the membranes are incubated with Azilsartan for 90 minutes, then immediately washed twice with 200 μL/well of assay buffer to remove unbound compounds, and further incubated for 5 hours with 125I-Sar1-Ile8-AII. Membrane-bound radioactivity is counted using a TopCount Microplate Scintillation and Luminescence Counter. In the experiments to estimate the dissociation rate of Azilsartan from AT1 receptors, membranes are incubated for 90 minutes with Azilsartan at a concentration of 30 nM for Azilsartan. Azilsartan inhibits the specific binding of 125I-Sar1-Ile8-AII to human AT1 by approximately 90%. The membranes are then immediately washed twice with 200 μL/well of assay buffer and further incubated with 125I-Sar1-Ile8-AII for 240 minutes. Membrane-bound radioactivity is counted using the TopCount Microplate Scintillation and Luminescence Counterat 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes, or 240 minutes. Nonspecific binding of 125I-Sar1-Ile8-AII is estimated in the presence of 10 μM unlabeled AII. Unlabeled AII is added again after washout for the washout experiment. Specific binding is defined as total binding minus nonspecific binding.
Cell Assay:[1]
  • Cell lines

    COS-7 cells expressing human AT1 receptors

  • Concentrations

    0 μM -1 μM

  • Incubation Time

    2 hours

  • Method

    Twenty-four hours after transfections, the COS-7 cells expressing human AT1 receptors are starved by changing the culture medium to starvation buffer (1 mM CaCl2, 0.5 mM MgCl2, 4.2 mM KCl, 146 mM NaCl, 5.5 mM glucose, and 10 mM HEPES, pH 7.3). Then, 5 μL/well of Azilsartan dissolved in starvation buffer is added to the cells at the indicated concentrations, and they are pretreated for the indicated times. Two hours after starvation, LiCl is added to a final concentration of 50 mM with or without AII 10 nM, and the cells are further incubated for the indicated times at 37°C. In washout experiments, the cells are washed once with 100 μL/well of starvation buffer to remove unbound Azilsartan before stimulation with AII. The accumulation of inositol 1-phosphate (IP1) is measured by using an IP-One Tb kit. The fluorescence resonance energy transfer signal is measured on a plate reader.
Animal Study:[4]
  • Animal Models

    Male Wistar-Kyoto (WKY) rats, obese Koletsky (fak/fak) rats

  • Dosages

    1 mg/kg, 2 mg/kg and 3 mg/kg

  • Administration

    Oral gavage

Customer Product Validation

Data from [Data independently produced by , , Scientific Reports, 2015, 5:8116.]

Selleck's Azilsartan has been cited by 3 publications

Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling [ Front Pharmacol, 2021, 12:774709] PubMed: 34899338
Degradation of SARS-CoV-2 receptor ACE2 by tobacco carcinogen-induced Skp2 in lung epithelial cells [ bioRxiv, 2020, 10.1101/2020.10.13.337774] PubMed: None
Suppression of adrenal barrestin3-dependent aldosteroneproduction by ARBs: head-to-head comparison [Dabul S, et al. Sci Rep, 2015, 5:8116] PubMed: 25631300

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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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