| Description | NS3623 is an activator of human ether-a-go-go-related gene potassium channels. NS3623 has a dual mode of action, being an inhibitor of hERG1 channels. NS3623 activates the IKr and Ito currents and has an antiarrhythmic effect. |
| In vitro | The application of NS3623 (5 μM) greatly increases the size of the tail current confirming previous studies demonstrating this drug increased IKr, in isolated canine cardiomyocytes. NS3623 enhances IKr tail currents (at +50 mV activating pulse) by 60% in normal Mid cells, and 68% in 48 h cultured cells. The effect of NS3623 on IKr recorded from cells kept in culture is evaluated. The magnitude of IKr is greatly decreased compared to freshly isolated cells, after 48 h. Peak IKr tail currents are 0.47 ± 0.08 pA/pF in freshly isolated myocytes and 0.28 ± 0.06 pA/pF in 2-day cultured myocytes. Application of NS3623 increases IKr in cultured Mid cells. Analysis of the current-voltage (I-V) relation of IKr tail current showed that NS3623 increased current density in both 1 day and 2-day cultured Mid cells [3]. |
| In vivo | NS3623 (30 mg/kg; i.v.; lasting for 3 minutes) shortens the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs.NS3623 (50 mg/kg) immediately reduces the QTcF interval and remains obviously shortened for approximately 30 minutes. NS3623 (50 mg/kg) shortens the QT interval by 30 +/- 6% in conscious guinea pigs [1]. |
| molecular weight | 427.18 |
| Molecular formula | C15H10BrF3N6O |
| CAS | 343630-41-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 9.17 mg/ml (21.46 mM) |
| References | 1. Hansen RS, et al. In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig. J Cardiovasc Pharmacol. 2008 Jul;52(1):35-41. 2. Diness JG, et al. Antiarrhythmic effect of IKr activation in a cellular model of LQT3. Heart Rhythm. 2009 Jan;6(1):100-6. 3. Calloe K, et al. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials. Biochem Pharmacol. 2016 May 15;108:36-46. 4. Hansen RS, et al. Biophysical characterization of the new human ether-a-go-go-related gene channel opener NS3623 [N-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-N'-(3'-trifluoromethylphenyl)urea]. Mol Pharmacol. 2006 Oct;70(4):1319-29. |