Imarikiren
Imarikiren (AK-272 free base) is an orally active, selective Renin inhibitor with an IC50 value of 2.1 nM against h-Renin. Imarikiren blocks the conversion of Angiotensinogen to Angiotensin I and reduces mean arterial pressure by inhibiting Angiotensin II that binds to AT1. Imarikiren alleviates myocardial hypertrophy and pulmonary congestion, exerting cardioprotective effects. Imarikiren can be used in research related to hypertension and heart failure.
For research use only. We do not sell to patients.
- CAS No.: 1202265-63-1
- Formula: C27H41N5O4
- Molecular Weight:499.65
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
[1]|
AT1 Receptor |
In Vitro
Imarikiren potently inhibits endogenous plasma renin with an IC50 of 2.1 nM; it exhibits no significant inhibitory activity against pepsin or cathepsin D even at concentrations as high as 10 μM[1].
Imarikiren (0.5 nM-500 mM) potently inhibits plasma renin (with an IC50 of 2.1 nM) and mouse plasma renin (with an IC50 of 53 nM) in vitro[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
Imarikiren (30-300 mg/kg; p.o.; once daily; 36 days) prolongs survival in CSQ-tg heart failure mice in a dose-dependent manner, with the 300 mg/kg dose producing a statistically significant survival benefit[2].
Imarikiren (30-300 mg/kg; p.o.; once daily; 12-13 days, 16-17 days, or 19 days) at 300 mg/kg reduces cardiac hypertrophy, lung congestion, and plasma heart failure biomarkers, inhibits left ventricular systolic dysfunction, and reduces cardiomyocyte injury in CSQ-tg heart failure mice, while 100 mg/kg reduces lung congestion[2].
Imarikiren (300 mg/kg; p.o.) potently inhibits plasma renin activity in CSQ-tg heart failure mice without reducing systolic blood pressure[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:human-angiotensinogen and human-renin double transgenic (dTg)[1]
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Dosage:3 mg/kg; 10 mg/kg
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Administration:p.o.; single dose
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Result:Showed antihypertensive efficacy comparable to aliskiren 75 mg/kg at 5 hours post-administration at 3 mg/kg dose.
Exceeded antihypertensive efficacy of aliskiren 75 mg/kg at both 5 hours and 24 hours post-administration at 10 mg/kg dose.
Exhibited potent, dose-dependent, long-lasting antihypertensive effects.
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Animal Model:calsequestrin transgenic (CSQ-tg) hybrid (C57BL/6J × DBA/2N) F1 (female, 5 weeks old at treatment initiation)[2]
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Dosage:30 mg/kg; 100 mg/kg; 300 mg/kg
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Administration:p.o.; once daily; 36 days
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Result:Significantly prolonged survival at 300 mg/kg (P < 0.01 vs. vehicle).
Showed non-significant survival improvements at 30 mg/kg (P = 0.42 vs. vehicle) and 100 mg/kg (P = 0.12 vs. vehicle).
Produced a dose-dependent survival benefit.
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Animal Model:calsequestrin transgenic (CSQ-tg) hybrid (C57BL/6J × DBA/2N) F1 (female, 5 weeks old at treatment initiation); wild-type (WT) hybrid (C57BL/6J × DBA/2N) F1[2]
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Dosage:30 mg/kg; 100 mg/kg; 300 mg/kg
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Administration:p.o.; once daily; 12-13 days, 16-17 days, or 19 days
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Result:Reduced left ventricular weight to 132.3 mg, right ventricular weight to 37.8 mg, right atrial weight to 5.8 mg, and lung weight to 113.1 mg at 300 mg/kg (P < 0.005 vs. vehicle for all).
Reduced lung weight to 126.2 mg at 100 mg/kg (P < 0.025 vs. vehicle).
Reduced plasma NT-proBNP levels by 26% to 7.4 ng/mL at 300 mg/kg (P < 0.025 vs. vehicle).
Inhibited the decrease in left ventricular ejection fraction (LVEF) to 26.7% at 300 mg/kg (P < 0.01 vs. vehicle).
Reduced plasma cardiac troponin I (cTnI) levels and attenuated upregulation of cardiac NADPH oxidase 4 (Nox4) mRNA and downregulation of cardiac nitric oxide synthase 3 (Nos3) mRNA at 300 mg/kg (P < 0.05 vs. vehicle for all).
Did not alter expression of fibrosis markers TGF-β1 or Col1α1 mRNA at 300 mg/kg.
Chemical Information
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CAS No. 1202265-63-1
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Molecular Weight 499.65
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Formula C27H41N5O4
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SMILES
COCCCCN1C(C(N([C@H]2C[C@H](CNC2)C(N3CCOCC3)=O)CC(C)C)=O)=NC4=CC=CC=C41
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Synonyms
AK-272 free base; SCO-272 free base
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Cardiovascular Diseases
Cardiovascular disease can be modeled as maladaptive cardiac remodeling, where ischemic injury or pressure overload activates inflammatory signaling, fibroblast activation, extracellular-matrix deposition, cardiomyocyte hypertrophy, vascular remodeling, and progressive ventricular dysfunction. The TGF-β/SMAD axis is a central profibrotic pathway after myocardial injury and pressure overload, while innate immune and cytokine pathways regulate leukocyte recruitment, scar formation, and adverse remodeling. Key unresolved questions include which inflammatory signals are reparative versus harmful, when fibrosis is protective versus maladaptive, and whether pathway inhibition improves function without weakening necessary infarct healing or compensatory remodeling.
Purity & Documentation
References
[1]. Imaeda Y, et al. Discovery of TAK-272: A Novel, Potent, and Orally Active Renin Inhibitor. ACS medicinal chemistry letters. 2016 Oct 13;7(10):933-938. [Content Brief]
[2]. Hara T, et al. TAK-272 (imarikiren), a novel renin inhibitor, improves cardiac remodeling and mortality in a murine heart failure model. PloS one. 2018;13(8):e0202176. [Content Brief]
[3]. Gebremichael Y, et al. Benchmarking renin suppression and blood pressure reduction of direct renin inhibitor imarikiren through quantitative systems pharmacology modeling. Journal of pharmacokinetics and pharmacodynamics. 2019 Feb;46(1):15-25. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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