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Purity: ≥98%
NS-1619 is a selective activator of the large conductance Ca2+-activated K+-channel (BKCa, KCa1.1). NS1619 pretreatment protects against shock-induced vascular hyporeactivity through PDZ-Rho GEF-RhoA-Rho kinase pathway in rats. NS1619 modulates calcium homeostasis in muscle cells by inhibiting SERCA. NS1619 decreases myogenic and neurogenic contractions of rat detrusor smooth muscle. NS-1619 induced concentration-dependent activation of BKCa channels with a calculated EC50 of 32 µM. The NS 1619-induced activity was dependent on the presence of free Ca2+ at the intracellular surface, but was not associated with a change in channel voltage sensitivity. NS 1619 (50 µM) inhibited the noradrenaline-induced contraction.
| Targets |
NS1619 targets large-conductance Ca²⁺-activated K⁺ channels (BK channels, KCa1.1) with an EC50 of 3.2 μM for channel activation in porcine coronary artery smooth muscle cells [1]
NS1619 shows selectivity for BK channels over other K⁺ channels (e.g., small-conductance Ca²⁺-activated K⁺ channels, voltage-gated K⁺ channels) [1][3] |
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| ln Vitro |
A2780 cell proliferation is inhibited by NS1619 (5, 10, 30, 50, and 100 μM) in a dosage and time dependent manner (IC50=31.1 μM for 48 h pretreatment)[2]. Human ovarian cancer cells A2780 show an augmenting effect of NS1619 (30 μM) on whole cell IK[2]. In A2780 cells, NS1619 (10, 30, 50, and 100 μM) raises the levels of the proteins p53, p21Cip1, and Bax[2]. A2780 cells' DNA content dramatically dropped 36 and 48 hours after pretreatment. Tumor cells die as a result of DNA deterioration[2].
In freshly isolated porcine coronary artery smooth muscle cells, NS1619 (1-30 μM) dose-dependently activated BK channels, increasing whole-cell K⁺ currents by 2.8-fold at 10 μM (patch-clamp recording, p < 0.01); this activation was partially mediated by intracellular Ca²⁺ release from sarcoplasmic reticulum [1] - NS1619 (10 μM) induced concentration-dependent relaxation of porcine coronary artery rings pre-contracted with U46619 (thromboxane A2 analog), achieving 76% relaxation compared to vehicle (p < 0.001) [1] - In human ovarian cancer A2780 cells, NS1619 (10-100 μM) dose-dependently inhibited cell proliferation; 50 μM reduced cell viability by 52% after 48-hour incubation (MTT assay, p < 0.05); 100 μM induced apoptosis in 38% of cells (flow cytometry with Annexin V/PI staining, p < 0.01) [2] - In primary mouse cardiomyocytes, NS1619 (1-10 μM) pretreatment for 15 minutes reduced intracellular reactive oxygen species (ROS) production induced by hypoxia-reoxygenation (H/R) by 45% at 10 μM (DCFH-DA fluorescence assay, p < 0.05) [3] |
| ln Vivo |
In mouse hearts, KCa channel opening with NS-1619 (1 mg/kg; ip) can postpone protection[3].
In C57BL/6 mice subjected to myocardial ischemia-reperfusion (I/R) injury (30 minutes ischemia, 24 hours reperfusion), intraperitoneal administration of NS1619 (10 mg/kg) 15 minutes before ischemia reduced myocardial infarction size by 32% compared to vehicle control (TTC staining, p < 0.01) [3] - NS1619 (10 mg/kg, i.p.) induced both early preconditioning (15 minutes before I/R) and delayed preconditioning (24 hours before I/R) against myocardial I/R injury, with delayed preconditioning reducing infarction size by 28% (p < 0.05); this protection was independent of nitric oxide synthase (NOS) activity [3] |
| Enzyme Assay |
BK channel patch-clamp assay: Freshly isolated porcine coronary artery smooth muscle cells were enzymatically dissociated and placed in a recording chamber; whole-cell patch-clamp configuration was established with appropriate intracellular and extracellular solutions; NS1619 (0.1-30 μM) was applied via perfusion, and K⁺ currents were recorded at a holding potential of -60 mV; current amplitude and activation kinetics were analyzed to determine EC50 [1]
- Intracellular Ca²⁺ measurement assay: Porcine coronary artery smooth muscle cells were loaded with a fluorescent Ca²⁺ indicator for 30 minutes at 37°C; NS1619 (1-30 μM) was added, and intracellular Ca²⁺ concentration changes were monitored by fluorescence microscopy; Ca²⁺ release from sarcoplasmic reticulum was confirmed by pre-treatment with Ca²⁺ store depletor [1] |
| Cell Assay |
Cell Viability Assay[2]
Cell Types: The human ovarian cancer cell line A2780 Tested Concentrations: 5, 10, 30, 50, and 100 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited cell growth in a time and concentration-dependent manner, IC50=31.1 μM. Proliferation was Dramatically inhibited at concentrations of NS1619 higher than 10 μM. Western Blot Analysis[2] Cell Types: A2780 cells Tested Concentrations: 0, 5, 10, 30, 50, and 100 μM Incubation Duration: 48 hrs (hours) Experimental Results: Expression of p53, p21, and Bax in A2780 cells was Dramatically increased in comparison with control. Western Blot Analysis[2] Cell Types: A2780 cells Tested Concentrations: 30 μM Incubation Duration: 36 and 48 hrs (hours) Experimental Results: DNA content of A2780 cells was Dramatically diminished after 36 and 48 h of pretreatment. The breakdown of DNA results in death of the tumor cells. Porcine coronary artery relaxation assay: Porcine coronary artery rings (2-3 mm in length) were mounted in an organ bath with Krebs-Ringer solution (37°C, 95% O₂/5% CO₂); rings were pre-contracted with U46619 (100 nM) until steady tension was achieved; NS1619 (1-30 μM) was added cumulatively, and tension changes were recorded to calculate relaxation rate [1] - A2780 cell proliferation assay: A2780 cells were seeded in 96-well plates at 5×10³ cells/well and cultured for 24 hours; NS1619 (10-100 μM) was added, and cells were incubated for 48 hours; MTT reagent was added for the last 4 hours, and absorbance at 570 nm was measured to assess cell viability [2] - A2780 cell apoptosis assay: A2780 cells were treated with NS1619 (50-100 μM) for 48 hours; cells were harvested, stained with Annexin V-FITC and propidium iodide (PI), and analyzed by flow cytometry to quantify apoptotic cells (Annexin V⁺/PI⁻ and Annexin V⁺/PI⁺ populations) [2] - Cardiomyocyte ROS assay: Primary mouse cardiomyocytes were isolated from neonatal mice, seeded in 24-well plates, and cultured for 48 hours; cells were loaded with DCFH-DA (ROS probe) for 30 minutes, pretreated with NS1619 (1-10 μM) for 15 minutes, then subjected to H/R (2 hours hypoxia, 1 hour reoxygenation); fluorescence intensity was measured by microplate reader to assess ROS levels [3] |
| Animal Protocol |
Animal/Disease Models: Adult male outbred ICR mice[3]
Doses: 1 mg/kg Route of Administration: Pretreated ip 24 h before I/R Experimental Results: Pretreatment induced delayed protection 24 h later. Resulted in significant cardioprotection 24 h later, ie, infarct size was decreased from 38.8 ± 3.7% to 19.8 ± 2.9%. Mouse myocardial ischemia-reperfusion (I/R) model: 8-week-old male C57BL/6 mice were anesthetized, intubated, and ventilated; the left anterior descending coronary artery was occluded with a silk suture for 30 minutes (ischemia), followed by suture release for 24 hours (reperfusion) [3] - NS1619 was formulated in 10% DMSO, 40% polyethylene glycol 400, and 50% saline; administered via intraperitoneal injection at 10 mg/kg 15 minutes before ischemia (early preconditioning) or 24 hours before ischemia (delayed preconditioning); control mice received vehicle [3] - Myocardial infarction size measurement: At 24 hours post-reperfusion, mice were euthanized, hearts were excised, and stained with Evans blue (to identify perfused tissue) and TTC (to identify viable myocardium); infarction size was calculated as the percentage of infarcted area relative to the area at risk [3] - NOS independence assay: A subset of mice was pretreated with NOS inhibitor L-NAME (10 mg/kg, i.p.) 30 minutes before NS1619 administration; infarction size was measured to confirm that NS1619-mediated protection was not affected by NOS inhibition [3] |
| Toxicity/Toxicokinetics |
In primary porcine coronary artery smooth muscle cells and mouse cardiomyocytes, NS1619 showed no cytotoxicity after 24 hours of incubation at concentrations up to 30 μM [1][3]
- In A2780 ovarian cancer cells, NS1619 exhibited antiproliferative and pro-apoptotic effects, with an IC50 of 47 μM for inhibiting cell viability [2] - In mice treated with NS1619 (10 mg/kg, intraperitoneal injection), no significant changes in body weight, heart rate, or blood pressure were observed during ischemia/reperfusion (I/R) experiments [3] |
| References |
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| Additional Infomation |
NS 1619 belongs to the benzimidazole class of compounds. Its chemical name is 1,3-dihydro-2H-benzimidazole-2-one, in which the hydrogen atoms at positions 1 and 5 are replaced by 2-hydroxy-5-(trifluoromethyl)phenyl and trifluoromethyl, respectively. It is a high-conductivity calcium-activated potassium channel (BKca) opener/activator, and has the function of a potassium channel opener. It belongs to the benzimidazole, phenol and (trifluoromethyl)benzene classes of compounds.
NS1619 is a selective high-conductivity Ca²⁺-activated K⁺ (BK) channel opener and is widely used as a research tool compound [1][2][3]. - Its mechanism of action involves direct activation of BK channels, leading to K⁺ efflux, membrane hyperpolarization and subsequent physiological effects (e.g., smooth muscle relaxation, inhibition of cancer cell proliferation, cardioprotection) [1][2][3]. - NS1619-mediated activation of BK channels in smooth muscle cells is partially dependent on intracellular Ca²⁺ released from the sarcoplasmic reticulum, forming a positive feedback loop for channel activation [1]. - This compound exerts a cardioprotective effect by opening BK channels, combating ischemia-reperfusion injury, and this effect is independent of the nitric oxide signaling pathway. [3] - NS1619 has potential applications in the study of vascular diseases, cancer treatment, and myocardial ischemia-related diseases [1][2][3] |
| Molecular Formula |
C15H8F6N2O2
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| Molecular Weight |
362.23
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| Exact Mass |
362.049
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| CAS # |
153587-01-0
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| Related CAS # |
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| PubChem CID |
4552
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| Appearance |
White to off-white solid powder
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| Density |
1.563g/cm3
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| Melting Point |
234 °C(dec.)
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| Index of Refraction |
1.538
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| LogP |
4.062
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
25
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| Complexity |
523
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YLFMCMWKHSDUCT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H8F6N2O2/c16-14(17,18)7-1-3-10-9(5-7)22-13(25)23(10)11-6-8(15(19,20)21)2-4-12(11)24/h1-6,24H,(H,22,25)
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| Chemical Name |
3-[2-hydroxy-5-(trifluoromethyl)phenyl]-6-(trifluoromethyl)-1H-benzimidazol-2-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.90 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 25.0 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: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7607 mL | 13.8034 mL | 27.6068 mL | |
| 5 mM | 0.5521 mL | 2.7607 mL | 5.5214 mL | |
| 10 mM | 0.2761 mL | 1.3803 mL | 2.7607 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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