Antiarrhythmic agent-4
Antiarrhythmic agent-4 is an orally active cardiac ion channel modulator. Antiarrhythmic agent-4 selectively inhibits pathological late sodium current of the cardiac NaV1.5 channel (IC50 = 2.5 μM) while blocking the hERG (IKr) channel (IC50 = 1.5 μM). Antiarrhythmic agent-4 reduces intracellular sodium/calcium overload, prolongs the cardiac action potential, and avoids conduction block and negative inotropic effects. Antiarrhythmic agent-4 exhibits antiarrhythmic efficacy in an isoproterenol-induced atrial fibrillation model in isolated rabbit hearts and improves survival and cardiac function in a Doxorubicin (HY-15142A)-induced heart failure mouse model. Antiarrhythmic agent-4 can be used for research on atrial fibrillation and heart failure.
For research use only. We do not sell to patients.
- Formula: C19H21F3N2O2
- Molecular Weight:366.38
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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
IC50 & Target
[1]|
IKr |
Nav1.5 2.5 μM (IC50) |
Nav1.2 52.3 μM (IC50) |
Nav1.6 39.5 μM (IC50) |
In Vitro
Antiarrhythmic agent-4 (Compound 8b) (10 μM) is a selective inhibitor of late NaV1.5 in HEK293T cells with an IC50 of 2.5 μM, and a potent inhibitor of hERG channels in CHO cells with an IC50 of 1.5 μM[1].
Antiarrhythmic agent-4 exhibits high selectivity for cardiac late INa over non-cardiac NaV1.X subtypes, with IC50 values exceeding 100 μM for NaV1.1, NaV1.3, NaV1.4, and NaV1.7, and moderate inhibitory activity against NaV1.2 and NaV1.6[1].
Antiarrhythmic agent-4 exhibits negligible inhibitory effect on CaV1.2 channels, with an IC50 of 287.9 μM, suggesting a low risk of negative inotropic effects[1].
Antiarrhythmic agent-4 is predicted to bind well to the central pore of the NaV1.5 channel with a docking score of -9.769, forming key hydrogen bonds and π-π stacking interactions; it also exhibits an excellent binding score of -9.757 in the central pore region of the NaV1.6 channel[1].
Antiarrhythmic agent-4 exhibits dose-dependent anti-atrial fibrillation activity in the ISO-treated isolated rabbit heart model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | C0 | T1/2 | AUClast | AUCinf | CL | Vss | Cmax | Tmax | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 220 ng/mL | 5.49 h | 918 ng·h/mL | 958 ng·h/mL | 18.1 mL/min/kg | 7.38 L/kg | / | / | / |
| Mice[1] | 3 mg/kg | i.p. | / | 4.80 h | 2633 ng·h/mL | 2708 ng·h/mL | / | / | 437 ng/mL | 0.417 h | 94.2 % |
| Mice[1] | 3 mg/kg | p.o. | / | 5.02 h | 3046 ng·h/mL | 3156 ng·h/mL | / | / | 386 ng/mL | 0.667 h | 110.0 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6N (male, eight-week-old, injection of Doxorubicin (HY-15142A) (2.15 mg/kg) on days 1, 3, 4, 7, 10, 13, and 15)
[1] -
Dosage:5, 10, 30 mg/kg
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Administration:i.p.; daily; 16 days
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Result:Suppressed Doxorubicin-induced mortality and attenuated body weight decline over the 21-day observation period.
Improved stroke volume (SV), ejection fraction (EF), and fractional shortening (FS) to an extent comparable to 50 mg/kg Ranolazine (HY-B0280) at 30 mg/kg.
Was as effective as 50 mg/kg Ranolazine in mitigating the decline in SV, EF, and FS at 10 mg/kg.
Still significantly improved SV and decreased mortality and severe weight loss at 5 mg/kg.
Chemical Information
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Molecular Weight 366.38
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Formula C19H21F3N2O2
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SMILES
NC([C@H](CC)NCCOC1=CC=C(C2=CC=CC(C(F)(F)F)=C2)C=C1)=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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Antiarrhythmic agent-4 Related Classifications
HY-189366 Related Classifications
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