KRI-1177
KRI-1177 is a competitive, dipeptide human renin inhibitor with a Ki of 0.7 μM and an IC50 of 90 nM. The IC50 of KRI-1177 targeting cynomolgus monkey renin is 680 nM. KRI-1177 acts as an antihypertensive agent, angiotensin inhibitor and plasma renin activity inhibitor, which reduces systemic blood pressure and plasma angiotensin concentration. KRI-1177 exhibits a relatively long-lasting antihypertensive effect in cynomolgus monkeys and can be used for hypertension research.
For research use only. We do not sell to patients.
- CAS No.: 105186-68-3
- Formula: C37H45N5O6
- Molecular Weight:655.80
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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
Biological Activity
Description
In Vitro
KRI-1177 (0.5 μM; 30 min) potently and selectively inhibits primate (human, Japanese monkey) plasma renin activity in vitro, with competitive inhibition of purified human renin (Ki = 0.7 μM), and far weaker inhibition of non-primate plasma renin and other proteolytic enzymes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
KRI-1177 (0.1-5 mg/kg; i.v.; single bolus injection) produces only a slight, transient hypotensive effect (~12 mmHg fall in mean blood pressure at 5 mg/kg i.v.) in anesthetized Japanese monkeys on a normal diet[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Japanese monkey (Macaca fuscata) (both sexes, 6-9 kg, hypertension model via low sodium diet for 1 week, furosemide pretreatment, anesthetized with pentobarbital sodium)[1]
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Dosage:0.1 mg/kg; 0.5 mg/kg; 1 mg/kg; 2.5 mg/kg; 5 mg/kg
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Administration:i.v.; single bolus injection
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Result:Produced a dose-dependent fall in systemic blood pressure.
Attained maximal hypotensive response of ~25 mmHg fall in mean blood pressure 5 minutes after 5 mg/kg i.v. injection, with half-maximal response restoration time of approximately 15 minutes.
Reduced plasma renin activity from pre-treatment mean of ~28 ng ANG I/mL per h to ~10 ng ANG I/mL per h after 1 mg/kg i.v. injection.
Reduced plasma renin activity from pre-treatment mean of ~50 ng ANG I/mL per h to ~5 ng ANG I/mL per h after 5 mg/kg i.v. injection.
Decreased plasma ANG I concentrations by 51.4% (from 1.62 ng/mL to 0.72 ng/mL) after 5 mg/kg i.v. injection.
Decreased plasma ANG II + III concentrations by 49.6% (from 149 pg/mL to 72 pg/mL) after 5 mg/kg i.v. injection.
Did not significantly alter heart rate at 5 mg/kg i.v.
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Animal Model:Japanese monkey (Macaca fuscata) (both sexes, 6-9 kg, normotensive, fed normal diet, anesthetized with pentobarbital sodium)[1]
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Dosage:0.1 mg/kg; 0.5 mg/kg; 1 mg/kg; 2.5 mg/kg; 5 mg/kg
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Administration:i.v.; single bolus injection
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Result:Induced a slight and transient fall in systemic blood pressure.
Attained maximal hypotensive response of ~12 mmHg fall in mean blood pressure 2 minutes after 5 mg/kg i.v. injection.
Chemical Information
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CAS No. 105186-68-3
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Molecular Weight 655.80
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Formula C37H45N5O6
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SMILES
O=C(OC)C(O)C(NC(=O)C(NC(=O)C(CC(=O)NCCC=1C=CC=CC1)CC2=CC=CC=3C=CC=CC32)CC4=CN=CN4)CC(C)C
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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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KRI-1177 Related Classifications
HY-119036 Related Classifications
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