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.
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- CAS. Nr.: 128053-53-2
- Formel: C38H51N5O7
- Molecular Weight:689.84
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
Beschreibung
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.
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. Nr. 128053-53-2
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Molecular Weight 689.84
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Formel 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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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[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
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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