| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| Targets |
The primary targets of NS3623 include hERG1 (KV11.1) potassium channels and red blood cell chloride conductance. It acts as an activator of hERG1 channels with an EC50 of 79.4 μM and as a blocker of red blood cell chloride conductance with an IC50 of 210 nM. The compound activates the IKr and Ito currents and has antiarrhythmic effects. hERG channels are voltage-gated potassium channels that play a critical role in the repolarization of cardiac action potentials. Activation of hERG channels can shorten the action potential duration and reduce the risk of arrhythmias. NS3623 has a dual mode of action, being both an activator and an inhibitor of hERG1 channels. The compound has also been reported to function as a selective inhibitor of EGFR.
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| 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
In vitro, NS3623 activates hERG1 channels with an EC50 of 79.4 μM and blocks red blood cell chloride conductance with an IC50 of 210 nM. The compound activates the IKr and Ito currents and has antiarrhythmic effects. NS3623 has a dual mode of action, being both an activator and an inhibitor of hERG1 channels. The compound's activity is typically measured using electrophysiological recordings (e.g., patch-clamp) in cells expressing hERG1 channels or using chloride flux assays in red blood cells. These assays confirm that NS3623 engages its targets and produces the expected effects on ion channel activity and chloride conductance. |
| 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].
In vivo, NS3623 has antiarrhythmic effects due to its activation of hERG1 channels and modulation of IKr and Ito currents. The compound's dual mode of action—activating hERG1 channels while also inhibiting them—may provide a unique therapeutic profile for the treatment of cardiac arrhythmias. The compound has also been investigated for the treatment of non-small cell lung cancer and other EGFR-driven malignancies. While specific in vivo efficacy data for NS3623 are not extensively detailed in the available literature, its mechanism of action suggests that it would be effective in modulating cardiac electrophysiology and potentially inhibiting tumor growth. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for NS3623 involve electrophysiological recordings using patch-clamp or two-electrode voltage clamp techniques in cells expressing hERG1 channels. In these assays, NS3623 is applied to cells, and the amplitude of hERG-mediated currents is measured. The EC50 for channel activation (79.4 μM) is determined from dose-response curves. Chloride flux assays using red blood cells are employed to measure the compound's inhibition of chloride conductance, with an IC50 of 210 nM. EGFR kinase assays can be performed to assess the compound's activity against EGFR. These assays confirm that NS3623 engages its targets and produces the expected effects.
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| Cell Assay |
In vitro cellular assays for NS3623 are conducted in cells expressing hERG1 channels (e.g., HEK293 cells) or in red blood cells. Cells are treated with varying concentrations of NS3623, and channel activity is assessed using electrophysiological recordings or chloride flux assays. The compound's effects on cell proliferation in EGFR-driven cancer cell lines can be assessed using MTT or CellTiter-Glo assays. These assays confirm that NS3623 engages its targets in a cellular context and produces the expected effects on ion channel activity, chloride conductance, and cell proliferation.
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| 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%. In vivo animal studies for NS3623 would typically be conducted in animal models of cardiac arrhythmias or cancer. In arrhythmia models, animals would be administered the compound, and cardiac electrophysiology would be monitored using electrocardiography (ECG) to assess the compound's antiarrhythmic effects. In cancer models, xenograft studies using EGFR-driven tumor cell lines would be performed to assess the compound's antitumor activity. These studies would confirm that NS3623 is effective in vivo and provide information about its therapeutic potential. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NS3623 indicate that it has a molecular weight of 427.18 and a molecular formula of C15H10BrF3N6O. The compound is soluble in DMSO at concentrations >10 mM, facilitating its use in in vitro assays and formulation for in vivo administration. For storage, the powder should be kept at 4°C. The compound's purity is typically high, ensuring quality and reproducibility in experimental studies.
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| Toxicity/Toxicokinetics |
The toxicological profile of NS3623 is primarily derived from its use as a research compound in preclinical studies. As a modulator of hERG channels, potential on-target effects could include changes in cardiac repolarization, which could lead to arrhythmias. The compound's dual mode of action—both activating and inhibiting hERG1 channels—may provide a unique safety profile. Comprehensive toxicology studies would be required for therapeutic development, including assessments of cardiac, neurological, and hematological function.
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| References |
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| Additional Infomation |
NS3623 is an activator of hERG1 potassium channels and a blocker of red blood cell chloride conductance. It has an EC50 of 79.4 μM for hERG1 channel activation and an IC50 of 210 nM for red blood cell chloride conductance inhibition. NS3623 activates the IKr and Ito currents and has antiarrhythmic effects. It has a dual mode of action, being both an activator and an inhibitor of hERG1 channels. The compound has also been reported to function as a selective inhibitor of EGFR. NS3623 is not approved for clinical use and is available from research chemical suppliers for preclinical studies.
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| Molecular Formula |
C15H10BRF3N6O
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| Molecular Weight |
427.19
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| Exact Mass |
426.005
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| CAS # |
343630-41-1
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| PubChem CID |
9954236
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| Appearance |
White to off-white solid powder
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| LogP |
4.378
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
497
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JXPULDIATMTIIN-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
1-[4-bromo-2-(2H-tetrazol-5-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea
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| Synonyms |
NS-3623 NS 3623 NS3623
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~585.23 mM)
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| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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