NS3623 (NS-3623) is a novel and potent (hERG) and KV4.3 channel activator with antiarrhythmic effects. It activates the IKr and Ito currents, also acts as a partial blocker of KV11.1 channels.
Physicochemical Properties
| Molecular Formula | C15H10BRF3N6O |
| Molecular Weight | 427.19 |
| Exact Mass | 426.005 |
| CAS # | 343630-41-1 |
| PubChem CID | 9954236 |
| Appearance | White to off-white solid powder |
| LogP | 4.378 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 26 |
| Complexity | 497 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | JXPULDIATMTIIN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C15H10BrF3N6O/c16-9-4-5-12(11(7-9)13-22-24-25-23-13)21-14(26)20-10-3-1-2-8(6-10)15(17,18)19/h1-7H,(H2,20,21,26)(H,22,23,24,25) |
| Chemical Name | 1-[4-bromo-2-(2H-tetrazol-5-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea |
| Synonyms | NS-3623 NS 3623 NS3623 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Application of NS3623 (5 μM) dramatically increased wake size in cultured isolated canine cells, validating earlier research indicating this medication raises IKr. Additionally, the impact of NS3623 on cellular IKr was assessed. When compared to newly isolated cells, the size of IKr was considerably less after 48 hours. After two days of culture, the peak IKr wake flow of cardiomyocytes was 0.28±0.06 pA/pF, while the peak IKr wake flow of freshly separated cells was 0.47±0.08 pA/pF. Applying NS3623 to cultured intermediate cells raised their IKr. Examination of the IKr wake's current-voltage (IV) relationship revealed that NS3623 had |
| ln Vivo | NS3623 (30 mg/kg; intravenously; for 3 minutes) corrected the QT period to 25 ± 4% in guinea pigs under anesthesia [1]. NS3623 (50 mg/kg) rapidly causes QT phase cycling in conscious guinea pigs and dramatically reduces the QTcF interval by around half an hour [1]. |
| Animal Protocol |
Animal/Disease Models: Anesthetized guinea pigs [1] Doses: 30 mg/kg Route of Administration: intravenous (iv) (iv)injection; 30±6%. Lasts 3 minutes Experimental Results:Corrected QT interval shortened by 25 +/- 4%. |
| References |
[1]. 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]. Antiarrhythmic effect of IKr activation in a cellular model of LQT3. Heart Rhythm. 2009 Jan;6(1):100-6. [3]. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials. Biochem Pharmacol. 2016 May 15;108:36-46. [4]. 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~585.23 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3409 mL | 11.7044 mL | 23.4088 mL | |
| 5 mM | 0.4682 mL | 2.3409 mL | 4.6818 mL | |
| 10 mM | 0.2341 mL | 1.1704 mL | 2.3409 mL |