ICI-170777
ICI-170777 is an orally active cardiotonic agent and type III Phosphodiesterase inhibitor, with an IC50 of 2.5 μM against cyclic AMP phosphodiesterase type III from canine cardiac fractions. ICI-170777 inhibits Aldrin epoxidase and pentobarbital metabolism. It enhances β-adrenergic receptor-mediated positive inotropic effects without causing chronotropic effects, while also exerting balanced arteriolar/venular vasodilator, platelet aggregation inhibitor and smooth muscle relaxant activities. ICI-170777 restores cardiac function in an acute canine heart failure model, exhibits additive effects when combined with Ouabain (HY-B1457), and shows no significant activity against multiple receptor classes or non-cardiac systems. ICI-170777 can be used in research related to congestive heart failure.
For research use only. We do not sell to patients.
- CAS No.: 123297-52-9
- Formula: C9H9N3OS
- Molecular Weight:207.25
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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
- Purity & Documentation
- References
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Help & FAQs
All Adrenergic Receptor Isoforms
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Biological Activity
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β adrenergic receptor |
ICI-170777 potently inhibits fraction III phosphodiesterase isolated from dog ventricular tissue with an IC50 of 2.5 μM[3].
ICI-170777 (10-7-10-4 M) exerts a concentration-dependent β-adrenoceptor-independent positive inotropic effect on cat isolated papillary muscles[3].
ICI-170777 (10-7-10-6 M) potently inhibits ADP (HY-W010918)- or collagen-induced in vitro platelet aggregation at concentrations of 10-7 M to 10-6 M[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Tmax | Bioavailability | T1/2 |
|---|---|---|---|---|---|
| Rat[3] | 5 mg/kg | p.o. | 1.5 h | 75 % | 4 h |
ICI-170777 (1-12.5 mg/kg; p.o.; daily; 10 days) inhibits rat hepatic microsomal aldrin epoxidase activity at doses of 4 mg/kg and higher when administered daily for 10 days, with no inhibition observed at 1 or 2 mg/kg[1].
ICI-170777 (1-80 mg/kg; p.o.; single dose) dose-dependently prolongs pentobarbitone-induced sleeping time in rats, with significant inhibition starting at 4 mg/kg, and the inhibitory effect persists for up to 24 hours post-dose[1].
ICI-170777 (10 μg/kg-5000 μg/kg; i.v.; cumulative dosing) produces dose-dependent positive inotropic effects in chloralose-anaesthetized dogs, with atenolol pretreatment attenuating but not abolishing the response, requiring a mean dose of 1.82 mg/kg i.v. to evoke a 50% increase in left ventricular dP/dtmax[2].
ICI-170777 (2-10 mg/kg; 5 mg/kg; p.o.; single dose; twice daily; 5 days) exerts a dose-dependent positive inotropic effect with minimal heart rate increase, balanced vasodilation, no tachyphylaxis, and a long duration of action in conscious dogs[3].
ICI-170777 (50 μg/kg/min; i.v.; continuous infusion) reverses ethanol-induced acute left ventricular dysfunction in anaesthetised dogs by reducing cardiac filling pressure and increasing cardiac output[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Alpk: APfSD albino rats (male, 160-252 g)[1]
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Dosage:5 mg/kg; 20 mg/kg; 80 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Reduced hepatic microsomal aldrin epoxidase activity to 5.9 nmol/mg/min at 5 mg/kg (P < 5%).
Reduced hepatic microsomal aldrin epoxidase activity to 3.1 nmol/mg/min at 20 mg/kg (P < 0.1%).
Reduced hepatic microsomal aldrin epoxidase activity to 1.7 nmol/mg/min at 80 mg/kg (P < 0.1%).
Caused no significant changes in total cytochrome P450 levels at any dose.
Reduced ethoxycoumarin O-deethylase activity to 0.17 pmol/mg/min only at 80 mg/kg (P < 5%).
Increased ethoxyresorufin O-deethylase activity to 24 pmol/mg/min only at 80 mg/kg (P < 1%).
Showed no obvious changes in P450 isozyme profile via SDS-PAGE.
Decreased daily body weight gain in the 80 mg/kg group during the first few days of treatment.
Caused no significant effect on liver weight relative to body weight at any dose.
Chemical Information
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CAS No. 123297-52-9
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Molecular Weight 207.25
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Formula C9H9N3OS
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SMILES
O=C1SC(C)C(C2=CC=NC=C2)=NN1
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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.
Purity & Documentation
References
[1]. McKillop D, et al. Different inhibition and induction profiles of hepatic drug metabolism in rats and dogs by two structurally related pyridyl diazinone cardiotonic agents. Biochem Pharmacol. 1991 Feb 1;41(3):411-7. [Content Brief]
[2]. Collis MG, et al. The cardiovascular pharmacology of ICI 170777 ((6RS)-6-methyl-5-(pyrid-4-yl)-3H,6H-1,3,4- thiadiazin-2-one) a novel compound with positive inotropic and vasodilator effects. Br J Pharmacol. 1989 Jun;97(2):409-18. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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