| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
EC50: 11.0 µM (BK channel)[1]
NS19504 targets large-conductance Ca2+-activated potassium channels (BK channels, also known as BKCa, KCa1.1, or MaxiK). It acts as a positive modulator with an EC50 of 11.0 uM. NS19504 shows a favorable selectivity profile, displaying no effect on contractions induced by high K+ concentration or at 65 other receptors tested, including L- and N-type Ca2+ channels, voltage-gated sodium channels (Nav), ATP-sensitive potassium channels (KATP), and hERG channels, indicating high selectivity for BK channels. |
|---|---|
| ln Vitro |
In newly isolated guinea pig bladder smooth muscle cells and whole-cell preparations, NS19504 enhances BK currents. The whole-cell current response to NS19504 is increased to 127%, 194%, 258%, and 561 % of control at 0.32 µM, 1.0 µM, 3.2 µM, and 10 µM, respectively[1].
In vitro, NS19504 activates BK channels in native smooth muscle cells isolated from guinea pig bladder. It reduces spontaneous phasic contractions in bladder strips ex vivo. The compound selectively activates BK channels with an EC50 of 11.0 uM. By enhancing BK channel activity, NS19504 promotes hyperpolarization and relaxation of smooth muscle cells. It has a relaxing effect on bladder smooth muscle spontaneous phasic contractions and shows no effect on contractions induced by high K+ concentration. |
| ln Vivo |
In vivo, NS19504 has been studied for its potential to treat bladder dysfunction, such as overactive bladder, by relaxing bladder smooth muscle. Detailed in vivo efficacy data should be obtained from primary literature. The compound may be administered via intraperitoneal or oral routes in animal models of bladder dysfunction. Its favorable selectivity profile over other ion channels (Nav, Cav, SK, IK, KATP, hERG) suggests a low risk of off-target effects.
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| Enzyme Assay |
To assess BK channel activation, HEK293 cells expressing BK channels (KCa1.1) are loaded with a voltage-sensitive or calcium-sensitive dye, or patch-clamp electrophysiology is used. Cells are pre-incubated with NS19504 at increasing concentrations (0.1-100 uM). Channel activity is measured by whole-cell or inside-out patch-clamp recordings. The EC50 for activation is calculated from dose-response curves. For selectivity assays, similar experiments are performed on cells expressing other potassium channels or ion channels.
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| Cell Assay |
For ex vivo tissue assays, bladder strips are dissected from guinea pigs or rats and mounted in organ baths filled with oxygenated Krebs solution. After equilibration, spontaneous phasic contractions are recorded isometrically. NS19504 (0.1-30 uM) is added cumulatively, and changes in contraction amplitude and frequency are measured. For cell-based assays, smooth muscle cells isolated from bladder are used. Cells are treated with NS19504 (1-100 uM), and intracellular calcium levels or membrane potential are measured using fluorescent dyes. Cell viability is assessed by MTT or LDH assay.
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| Animal Protocol |
For in vivo efficacy studies, NS19504 is formulated in an appropriate vehicle (e.g., 10% DMSO in saline or PEG400) and administered orally or intraperitoneally to rats or mice at doses ranging from 1-30 mg/kg. In models of overactive bladder (e.g., cyclophosphamide-induced cystitis or partial bladder outlet obstruction), drug is administered once daily for 1-2 weeks. Bladder function is assessed by cystometry, urine spot analysis, or measurement of micturition frequency. Smooth muscle relaxation can be assessed by in vivo measurement of intravesical pressure.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for NS19504 are limited in publicly available sources. The compound has a molecular weight of 269.16 and is described as a small molecule BK channel activator. For species-specific PK parameters (Cmax, Tmax, t1/2, oral bioavailability), researchers should consult the primary literature or conduct pilot studies. Solubility: NS19504 is soluble in DMSO (26.92 mg/mL). Standard formulation for in vivo studies involves dissolution in DMSO followed by dilution in saline or other vehicles.
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| Toxicity/Toxicokinetics |
Published toxicology data for NS19504 are limited. In ex vivo tissue assays, the compound shows no effect on contractions induced by high K+ concentration, indicating that it does not non-specifically affect smooth muscle contractility. It shows no activity on L- and N-type Ca2+ channels, Nav, KATP, or hERG channels at relevant concentrations, suggesting a low risk of cardiotoxicity. In animal studies at effective doses, no severe adverse events have been reported. Comprehensive toxicology studies are not publicly available.
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| References | |
| Additional Infomation |
NS19504 is a research tool compound and is not approved for clinical use. It is used as a pharmacological tool to study BK channel function in smooth muscle physiology and bladder dysfunction. Its high selectivity for BK channels over other ion channels makes it useful for dissecting BK channel-specific contributions to smooth muscle relaxation. The compound is also of interest for other BK channel-related conditions, such as hypertension and erectile dysfunction. NS19504 should be stored at -20degC as a powder, protected from light.
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| Molecular Formula |
C10H9BRN2S
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|---|---|
| Molecular Weight |
269.16
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| Exact Mass |
267.967
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| CAS # |
327062-46-4
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| PubChem CID |
727750
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.659
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
14
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| Complexity |
183
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1CC2=CN=C(S2)N)Br
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| InChi Key |
HGWLTZOMQZIUBW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H9BrN2S/c11-8-3-1-7(2-4-8)5-9-6-13-10(12)14-9/h1-4,6H,5H2,(H2,12,13)
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| Chemical Name |
5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine
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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: 100 mg/mL (371.53 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7153 mL | 18.5763 mL | 37.1526 mL | |
| 5 mM | 0.7431 mL | 3.7153 mL | 7.4305 mL | |
| 10 mM | 0.3715 mL | 1.8576 mL | 3.7153 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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