Irbesartan

Catalog No.S1507 Synonyms: BMS-186295, SR-47436

Irbesartan Chemical Structure

Molecular Weight(MW): 428.53

Irbesartan (SR-47436, BMS-186295) is a highly potent and specific angiotensin II type 1 (AT1) receptor antagonist with IC50 of 1.3 nM.

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2 Customer Reviews

  • Efficacy of ARBs at preventing StAR upregulation in SII-stimulated H295R cells. (A,B) Western blotting for StAR protein levels in H295R cells transfected to overexpress barr1 and treated for 6 hrs with 10 μM SII alone (SII) or in the presence of 10 μM of each of the sartans tested. Representative blots of 3 independent experiments are shown in (A), including blots for barr1 to confirm its overexpression and for GAPDH (glyceraldehyde 3-phosphate dehydrogenase) as loading control, and the StAR protein induction (as % of the SII response), as derived by densitometric quantification, is shown in (B). *, p <0.05, n=3 independent experiments/treatment. Blots shown have been cropped to fit space requirements and run under the same experimental conditions (same gel) (the full length blots are shown in Supplementary Information). (C,D) Western blotting for StAR protein levels in dominant negative barr1 mutanttransfected H295R cells and treated as in (A-B). Representative blots are shown in (C), including blots for the dominant negative barr1 mutant to confirm its overexpression and for GAPDH as loading control, and the StAR protein induction (as % of vehicle-no stimulation), as derived by densitometric quantification, is shown in (D). No significant differences were observed among treatments, nor did any treatment cause any induction in StAR levels. Blots shown have been cropped to fit space requirements and run under the same experimental conditions (same gel) (the full length blots are shown in Supplementary Information). n=3 independent experiments/treatment. LOS: Losartan-; VAL: Valsartan; CAN: Candesartan; OLM: Olmesartan; IRB: Irbesartan.

    Sci Rep, 2015, 5:8116.. Irbesartan purchased from Selleck.

    Immunofluorescence analysis of HBcAg expression at day 10 after irbesartan administration for HBV (genotype D) infection at MGE 200. The m47F peptide (400 nM) and ezetimibe (50 lM) were used as positive controls for HBV entry inhibition.

    Antiviral Res, 2015, 120:140-6.. Irbesartan purchased from Selleck.

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Biological Activity

Description Irbesartan (SR-47436, BMS-186295) is a highly potent and specific angiotensin II type 1 (AT1) receptor antagonist with IC50 of 1.3 nM.
Features Irbesartan is a longer acting AT1 receptor antagonist relative to losartan and valsartan.
Targets
AT1 receptor [1]
1.3 nM
In vitro

Irbesartan competes with angiotensin II (AII) for binding at the AT1 receptor subtype and antagonizes AII-induced contraction in rabbit aorta ring with IC50 of 4 nM. Irbesartan has no affinity for AT2 receptors. [1] Irbesartan (10 μM) blocks angiotensin II induced increase in αv, β1, β3, and β5 integrins, osteopontin, and α-actinin mRNA and protein levels in rat cardiac fibroblasts, leading to the decrease of cell attachment to extracellular matrix (ECM) proteins. [2] Irbesartan treatment markedly induces the expression of the adipogenic marker gene adipose protein 2 (aP2) in 3T3-L1 cells in a concentration-dependent manner with EC50 of 3.5 μM and 3.3-fold induction at the concentration of 10 μM. Irbesartan (10 μM) markedly induces transcriptional activity of the peroxisome proliferator–activated receptor-γ (PPARγ) by 3.4-fold independent of its AT1 receptor blocking action. [3] Pretreatment with Irbesartan (~10 μM) decreases angiotensin II-induced apoptosis in rat vascular smooth muscle cells by blocking angiotensin II internalization in a concentrationdependent manner. [4]

In vivo Oral administration of Irbesartan (1 mg/kg) reduces angiotensin II (AII)-induced hypertension, equipotent with losartan in conscious normotensive rats, markedly more active than losartan (10 mg/kg) in normotensive cynomolgus monkeys. [1] Administration of Irbesartan (7 mg/kg/day) significantly prevents skeletal muscle apoptosis and muscle atrophy in rats with monocrotaline-induced congestive heart failure (CHF), which is involved with the decrease of TNFα level and attributed to AT1 receptor blocking. [5]

Protocol

Animal Research:[1]
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  • Animal Models: Male Sprague-Dawley rats and female cynomolgus monkeys (Macaca fascicularis) injected (iv) with angiotensin II (AII)
  • Formulation: Dissolved in water by neutralization with a stoichiometric equivalent of KOH, or dissolved in saline by neutralization with a stoichiometric equivalent of L-arginine
  • Dosages: 1 mg/kg
  • Administration: Oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 4 mg/mL warmed (9.33 mM)
Ethanol 3 mg/mL (7.0 mM)
Water Insoluble
In vivo Add solvents individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
30 mg/mL

* 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 428.53
Formula

C25H28N6O

CAS No. 138402-11-6
Storage powder
Synonyms BMS-186295, SR-47436

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03016832 Not yet recruiting Diabetic Kidney Disease Jiangsu Famous Medical Technology Co., Ltd. January 2017 Early Phase 1
NCT02842359 Recruiting Type 2 Diabetes Mellitus Sanofi August 2016 Phase 4
NCT02597361 Recruiting Ehlers-Danlos Syndrome, Vascular Type Assistance Publique - Hôpitaux de Paris|Ministry of Health, France January 2016 Phase 3
NCT02644486 Recruiting Obesity and Glomerulopathy Zhi-Hong Liu, M.D.|Nanjing University School of Medicine January 2016 --
NCT02380625 Not yet recruiting Ebola Virus Disease Clinical Research Management, Inc.|Bill and Melinda Gates Foundation|Duke University|University of Sierra Leone|INC Research|University of North Carolina April 2015 Phase 1|Phase 2
NCT02386293 Recruiting Hypertension|Obesity|Stress, Psychological|Blood Pressure Augusta University September 2014 Phase 2

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