KRI-1314
KRI-1314 is an orally active human renin inhibitor with selectivity for primate renin over non-primate renin. KRI-1314 competitively inhibits the binding of recombinant human renin to its substrate, reduces plasma renin activity, lowers blood pressure, and exhibits high stability in tissue homogenates. KRI-1314 is applicable to research on renin-dependent hypertension and hypertension-related studies.
For research use only. We do not sell to patients.
- CAS No.: 128053-53-2
- Formula: C38H51N5O7
- Molecular Weight:689.84
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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-1314 (30 min) potently and selectively inhibits human plasma renin (IC50 = 1.8 nM) and shows decreasing inhibitory potency against plasma renin from Japanese monkeys, cynomolgus monkeys, rhesus monkeys, dogs, rabbits, guinea pigs, and rats[1].
KRI-1314 competitively inhibits purified human renin with a Ki value of 0.99 nM[1].
KRI-1314 strongly inhibits renin-like activities in kidney, adrenal, heart, lung, and aorta tissues from Japanese monkeys, with IC50 values ranging from 29 nM to 55 nM[1].
KRI-1314 is highly stable in liver, lung, small intestine, and kidney homogenates from Japanese monkeys, retaining full initial concentration after 4 hours of incubation at 37°C[1].
KRI-1314 potently inhibits human renin with an IC50 of 2.4 nM and does not significantly inhibit cathepsin D or chymotrypsin[2].
KRI-1314 competitively inhibits purified recombinant human renin with a Ki of 4.3 nM[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
KRI-1314 (10-30 mg/kg; oral administration; single dose via feeding tube) produces a maximum blood pressure reduction of approximately 20 mmHg, inhibits renin activity in a dose-dependent manner, and has no effect on heart rate; in sodium-depleted Japanese monkeys, its plasma concentration is maintained for at least 7 hours[1].
KRI-1314 (0.1 mL/kg per min; intravenous injection; infused for 10 min) dose-dependently inhibits recombinant human renin-induced hypertension in denervated SHR, with an ED50 of 0.81 mg/kg for intravenous administration[3].
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, 7 to 11 kg, sodium-depleted hypertension model)[1]
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Dosage:0.025 mg/kg; 0.05 mg/kg; 0.1 mg/kg; 0.25 mg/kg; 0.5 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:i.v.; single bolus injection
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Result:Produced dose-dependent blood pressure reduction ranging from 2.0 mmHg (0.025 mg/kg) to 17.5 mmHg (3 mg/kg) within 2-6 min post injection.
Reduced PRA by 88.9%-96.9% at peak hypotension for tested iv doses.
Suppressed PRA by 36.3%-81.9% at 30 min post injection alongside full blood pressure recovery.
Caused no obvious alteration to heart rate.
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Animal Model:Japanese monkey (Macaca fuscata) (both sexes, 7 to 11 kg, sodium-depleted hypertension model)[1]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; single administration via feeding tube
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Result:Showed negligible impacts on blood pressure and PRA after 3 mg/kg oral dosage.
Produced around 20 mmHg peak blood pressure drop at 3-4 h and time-dependent PRA suppression at 10 mg/kg.
Produced identical ~20 mmHg maximal hypotension at 3-4 h with stronger sustained PRA inhibition at 30 mg/kg.
Caused no remarkable shift in heart rate across all dosages.
Resulted in measurable plasma drug levels over 7 h, with stable concentrations corresponding to 10 and 30 mg/kg doses.
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Animal Model:Male SHR (16 weeks old, 300-350 g body weight)[3]
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Dosage:0.1 mL/kg per min
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Administration:intravenous injection; infused for 10 min
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Result:Dose-dependently inhibited recombinant human renin-induced hypertension in denervated SHR, with an ED50 of 0.81 mg/kg for intravenous administration.
Chemical Information
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CAS No. 128053-53-2
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Molecular Weight 689.84
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Formula C38H51N5O7
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SMILES
CC(C)OC([C@H](O)[C@H](CC1CCCCC1)NC([C@H](CC2=CN=CN2)NC([C@@H](CC(N3CCOCC3)=O)CC4=CC=CC5=C4C=CC=C5)=O)=O)=O
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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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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]. Etoh Y, et al. KRI-1314: an orally effective inhibitor of human renin. Jpn J Pharmacol. 1993;63(1):109-119. [Content Brief]
[3]. Shibasaki M, et al. The effect of intravenous recombinant human renin on blood pressure in pithed spontaneously hypertensive rats. Eur J Pharmacol. 1992;215(2-3):271-276. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KRI-1314 Related Classifications
HY-183978 Related Classifications
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