| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target of dabuzalgron is the α-1A adrenergic receptor (α1A-AR). It selectively binds to α1A-ARs over α1B- and α1D-ARs expressed in CHO-K1 cells with Ki values of 0.041, 1.6, and 6.5 µM, respectively. It acts as a partial agonist, selectively inducing inositol phosphate accumulation in α1A-AR-expressing cells with an EC50 of 0.204 µM.
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| ln Vitro |
Dabuzalgron selectively induces inositol phosphate accumulation in CHO-K1 cells expressing recombinant human α1A-ARs (EC50 = 0.204 µM) over those expressing α1B- or α1D-ARs (EC50 >100 µM for both). It induces urethral tension in rabbit bladder neck preparations with an EC50 of 0.363 µM. The compound exhibits functional M3/M2 selectivity in vivo and protects against doxorubicin-induced cardiotoxicity.
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| ln Vivo |
Intravenous administration of dabuzalgron increases intraurethral pressure and diastolic arterial pressure in anesthetized micropigs with ED50 values of 41 and 36 µg/kg, respectively. Oral administration at 10 µg/kg decreases cardiac contractility. At 300 µg/kg, it increases urethral tension without affecting diastolic arterial pressure or heart rate in conscious micropigs. It protects against doxorubicin-induced cardiotoxicity by preserving mitochondrial function.
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| Enzyme Assay |
For receptor binding assays, membrane fractions from CHO-K1 cells expressing recombinant human α1A-, α1B-, or α1D-ARs are incubated with increasing concentrations of dabuzalgron in the presence of a radiolabeled α1-adrenergic antagonist. Bound radioactivity is separated by filtration and quantified by scintillation counting. Ki values are calculated using the Cheng-Prusoff equation.
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| Cell Assay |
In cell-based assays, CHO-K1 cells expressing recombinant α1A-, α1B-, or α1D-ARs are loaded with a fluorescent calcium indicator or labeled with myo-[3H]inositol. Following stimulation with dabuzalgron, inositol phosphate accumulation is measured by ion-exchange chromatography. Urethral tension is assessed in isolated rabbit bladder neck preparations using organ bath studies.
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| Animal Protocol |
Animal studies employ anesthetized or conscious micropigs to assess cardiovascular and urological effects. Dabuzalgron is administered intravenously or orally at doses of 10-300 µg/kg. Intraurethral pressure, diastolic arterial pressure, and heart rate are continuously monitored. Doxorubicin-induced cardiotoxicity models are used to assess the protective effects of dabuzalgron on mitochondrial function and cardiac performance.
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| References | |
| Additional Infomation |
R450 is an α1-adrenergic receptor antagonist that works by tightening bladder muscle tone. It is currently under consideration for the treatment of stress urinary incontinence. Phase IIa clinical trial data showed that it reduced the frequency of incontinence episodes compared to placebo, with minimal cardiovascular side effects.
Drug Indications It is being investigated for the treatment of urinary incontinence. Mechanism of Action R450 is a selective α1-adrenergic receptor antagonist. Studies in the treatment of urinary incontinence suggest that it is likely an antagonist of α1B and α1D receptors, while also having an agonistic effect on α1a receptors. Pharmacodynamics R450 is an α1-adrenergic receptor antagonist that works by tightening bladder muscle tone. |
| Molecular Weight |
354.25268
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|---|---|
| Exact Mass |
353.037
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| CAS # |
219311-43-0
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| Related CAS # |
219311-44-1;219311-43-0 (HCl);
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| PubChem CID |
219093
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| Appearance |
White to off-white solid
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| Boiling Point |
521.1ºC at 760mmHg
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| Flash Point |
268.9ºC
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| Vapour Pressure |
5.88E-11mmHg at 25°C
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| LogP |
3.12
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
21
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| Complexity |
463
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.CS(NC1=C(Cl)C=CC(OCC2NCCN=2)=C1C)(=O)=O
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| InChi Key |
QFRMKDCRDUXTBR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H16ClN3O3S.ClH/c1-8-10(19-7-11-14-5-6-15-11)4-3-9(13)12(8)16-20(2,17)18;/h3-4,16H,5-7H2,1-2H3,(H,14,15);1H
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| Chemical Name |
N-[6-chloro-3-(4,5-dihydro-1H-imidazol-2-ylmethoxy)-2-methylphenyl]methanesulfonamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.8229 mL | 14.1143 mL | 28.2287 mL | |
| 5 mM | 0.5646 mL | 2.8229 mL | 5.6457 mL | |
| 10 mM | 0.2823 mL | 1.4114 mL | 2.8229 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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