P552-02
P552-02 is an epithelial sodium channel (ENaC) inhibitor. P552-02 blocks ENaC function in humans, guinea pigs, rats and sheep, exhibits the characteristic of reduced dissociation rate after binding to ENaC, inhibits ENaC-mediated short-circuit current, and slows the absorption of airway surface liquid (ASL). P552-02 induces hyperkalemia in guinea pigs and rats, blocks the activity of airway ENaC in guinea pigs, and enhances mucociliary clearance in sheep both in vivo and in vitro. P552-02 is applicable to cystic fibrosis-related research.
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- No. CAS: 587879-32-1
- Fòrmula: C19H26ClN7O4
- Peso molecular:451.91
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Descripciòn
In Vitro
P552-02 potently inhibits ENaC-mediated short-circuit current in primary human bronchial cells (pIC50 = 8.62), guinea pig ENaC (pIC50 = 8.42), and rat ENaC (pIC50 = 8.46), and exerts strong inhibitory activity against wild-type human ENaC in transfected FRT cells with a pIC50 of 8.85; mutations at the amiloride binding site drastically reduce its potency, with 4316-fold and 435-fold pIC50 shifts for αβG525Aγ and αβγG537C respectively[1].
P552-02 (250 nM; 2-10 min) exerts a moderately long-lasting blocking effect on ENaC in primary human bronchial epithelial cells, with 73.7% recovery of ISC after 2 min of incubation at 250 nM and 82.9% recovery after 10 min of incubation[1].
P552-02 potently inhibits ENaC-mediated short-circuit current in cultured human bronchial epithelial cells; it blocks the sustained absorption of airway surface liquid (ASL) in vitro, and acts synergistically with hypertonic saline to maintain the hydration state of ASL without blocking aquaporins[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | CL | Vss | T1/2 |
|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 149 mL/min/kg | 19.7 L/kg | 3.8 h |
In Vivo
P552-02 (200-2000 μg/kg; intratracheal administration; single dose) induces dose-dependent hyperkalemia in rats following intratracheal administration[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Dunkin Hartley (male, 300-650 g)[1]
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Dosage:0.2 μg/kg (TPD assessment at 1 h); 128 μg/kg (TPD assessment at 4 h)
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Administration:i.t.; single dose
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Result:Attenuated tracheal potential difference with an ED50 of 0.2 μg/kg at 1 h after dosing.
Retained airway ENaC-blocking activity with an ED50 of 128 μg/kg at 4 h after dosing.
Induced a significant elevation in blood potassium levels relative to vehicle control at doses ≥ 60 μg/kg.
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Animal Model:Sprague-Dawley (male, 250-350 g)[1]
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Dosage:200, 600, 2000 μg/kg
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Administration:i.t.; single dose
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Result:Induced significant increases in blood potassium levels relative to vehicle control at 600 μg/kg (mean maximum level 6.53 mmol/L) and 2000 μg/kg (mean maximum level 6.95 mmol/L).
Chemical Information
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No. CAS 587879-32-1
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Peso molecular 451.91
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Fòrmula C19H26ClN7O4
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SMILES
O=C(NC(=N)NCCCCC1=CC=C(OCC(O)CO)C=C1)C2=NC(Cl)=C(N=C2N)N
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
P552-02 Related Classifications
HY-187082 Related Classifications
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