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Purity: ≥98%
NS1652 is a novel, reversible anion conductance inhibitor which blocks chloride channel with an IC50 of 1.6 μM in human and mouse red blood cells. In vitro application of NS1652 lowers the net KCl loss from deoxygenated sickle cells from about 12 mmol/L cells/h to about 4 mmol/L cells/h, a value similar to that observed in oxygenated cells. Experiments performed in mice demonstrate that NS1652 is well tolerated and decreases red cell anion conductance in vivo. A low cation conductance and a high anion conductance are characteristic of normal erythrocytes. In sickle cell anemia, the polymerization of hemoglobin S (HbS) under conditions of low oxygen tension is preceded by an increase in cation conductance. This increase in conductance is mediated in part through Ca(++)-activated K(+) channels. A net efflux of potassium chloride (KCl) leads to a decrease in intracellular volume, which in turn increases the rate of HbS polymerization. Treatments minimizing the passive transport of ions and solvent to prevent such volume depletion might include inhibitors targeting either the Ca(++)-activated K(+) channel or the anion conductance.
| ln Vitro |
With human and mouse erythrocytes, NS1652 potently inhibits chloride conductance (IC50, 1.6 μM), but in HEK293 cells, it only weakly inhibits VRAC (IC50, 125 μM). At an IC50 of 3.1 μM, NS1652 dramatically inhibits the production of NO in BV2 cells. Additionally, NS1652 completely eliminates iNOS expression in BV2 cells at 10 μM after downregulating it at 3 μM [1]. Normal red blood cells experience increased hyperpolarization as a result of NS1652 (0, 1.0, 3.3, 10 and 20 μM) inhibiting their chloride conductance. When NS1652 is added, the net loss of KCl from deoxysickle cells decreases to about 4 mM cells/hour from about 12 mM cells/hour. Erythrocyte Cl conductance is totally and reversibly inhibited by NS1652 (20 μM) [2].
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| ln Vivo |
Mice's Cl- conductivity of erythrocytes can be blocked >90% by NS1652 (50 mg/kg, intravenous injection) [2].
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| References |
[1]. Kjaer K, et al. Chloride channel blockers inhibit iNOS expression and NO production in IFNgamma-stimulated microglial BV2 cells. Brain Res. 2009 Jul 24;1281:15-24.
[2]. Bennekou P, et al. Volume control in sickle cells is facilitated by the novel anion conductance inhibitor NS1652. Blood. 2000 Mar 1;95(5):1842-8 |
| Molecular Formula |
C₁₅H₁₁F₃N₂O₃
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| Molecular Weight |
324.25
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| CAS # |
1566-81-0
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| SMILES |
O=C(O)C1=CC=CC=C1NC(NC2=CC=CC(C(F)(F)F)=C2)=O
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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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0840 mL | 15.4202 mL | 30.8404 mL | |
| 5 mM | 0.6168 mL | 3.0840 mL | 6.1681 mL | |
| 10 mM | 0.3084 mL | 1.5420 mL | 3.0840 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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