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| Targets |
α-1A adrenergic receptor. Dabuzalgron is a selective α-1A adrenergic receptor agonist. It has an EC50 of 25 nM for the human cloned adrenergic α-1A receptor expressed in CHO cells. It shows selectivity over α-1B and α-1D receptors, with EC50 values >10,000 nM for these subtypes. It also shows selectivity over α-2A receptors, with an EC50 >10,000 nM.
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| ln Vitro |
Treatment with dabuzalgron elevated phosphorylation of ERK in a dose-dependent manner (EC50 = 4.8 μM). Dabuzalgron's cardioprotective properties are partly attributed to ERK1/2 activation [1]. The NRVM is shielded from doxorubicin (DOX)-induced cell death by dabuzalgron (10 μM; 4 hours) [1]. By activating α1A-AR, dabuzalgron (10 μM; 4 hours) prevents the activation of crucial components of the apoptotic response to mitochondrial injury and mitigates the detrimental effects of DOX on mitochondrial membrane potential [1].
Dabuzalgron activates the α-1A adrenergic receptor with an EC50 of 25 nM in CHO cells. It shows selectivity over α-1B, α-1D, and α-2A receptors. In vitro, Dabuzalgron treatment increases ERK phosphorylation. It protects against doxorubicin-induced cardiotoxicity by preserving mitochondrial function. |
| ln Vivo |
Through the activation of α1A-AR, dabuzalgron (10 μg/kg; oral gavage; twice daily; for 7 days; C57Bl6J wild-type or α1A-AR knockout mice) therapy reduces DOX cardiotoxicity. In the hearts of mice given DOX, dabuzalgron retains ATP content, upregulates PGC1α, inhibits the lowering of transcripts linked to mitochondrial function, and lessens oxidative stress [1].
Dabuzalgron is an orally active compound used for the treatment of urinary incontinence. It protects against doxorubicin-induced cardiotoxicity by preserving mitochondrial function. The compound has been discontinued in Phase 2 clinical trials for urinary incontinence. |
| Enzyme Assay |
Dabuzalgron is evaluated in cell-free receptor binding assays using membrane preparations expressing adrenergic receptor subtypes. Radioligand binding displacement assays are performed to determine the affinity and selectivity of Dabuzalgron for α-1A, α-1B, α-1D, and α-2A receptors. Competition binding experiments are conducted with increasing concentrations of Dabuzalgron and fixed concentrations of labeled reference ligands.
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| Cell Assay |
Western blot analysis[1]
Cell Types: Neonatal rat ventricular myocytes (NRVM) Tested Concentrations: 0.1 μM, 1 μM, 10 μM and 100 μM Incubation Duration: 15 minutes Experimental Results: ERK phosphorylation increased in a dose-dependent manner with an EC50 of 4.8 microns. Dabuzalgron is assessed in cell-based functional assays using CHO cells expressing human cloned adrenergic receptors. Calcium mobilization is measured using FLIPR to assess receptor activation. The compound shows an EC50 of 25 nM for α-1A receptors and EC50 values >10,000 nM for α-1B, α-1D, and α-2A receptors. |
| Animal Protocol |
Animal/Disease Models: Male C57Bl6J wild-type (WT) or α1A-AR knockout (AKO) mice (8-12 weeks old) were injected with doxorubicin (DOX) [1]
Doses: 10 μg/kg Route of Administration: po (oral gavage) Gastric; twice (two times) daily; for 7 days Experimental Results: Contractile function was preserved and fibrosis was diminished after administration of DOX. Compared with WT mice, AKO mice treated with DOX had worse survival rates and more severely impaired contractile function. Prevents the reduction of transcripts related to mitochondrial function, preserves ATP content, and reduces oxidative stress in the hearts of DOX-treated mice. Dabuzalgron is administered orally in animal models to evaluate its efficacy in treating urinary incontinence. It has been studied in preclinical models and has been in Phase 2 clinical trials. The compound protects against doxorubicin-induced cardiotoxicity. However, specific animal study protocols are not well-documented. |
| ADME/Pharmacokinetics |
Dabuzalgron is an orally active compound. It has a molecular weight of 317.79 and a molecular formula of C12H16ClN3O3S. It has a CAS number of 219311-44-1 and a UNII code of LGX4GZ74WO. The compound should be stored as a powder at -20°C for up to 3 years. Stock solutions should be stored at -80°C for up to 6 months.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is available for Dabuzalgron. The compound is for research use only and is not intended for human therapeutic use. It has been discontinued in Phase 2 clinical trials. The compound protects against doxorubicin-induced cardiotoxicity by preserving mitochondrial function.
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| References | |
| Additional Infomation |
Dabuzalgron is a sulfonamide drug, chemically named N-phenylmethanesulfonamide, with a chlorine atom attached at the 2-position, a 4,5-dihydro-1H-imidazol-2-ylmethoxy group at the 5-position, and a methyl group at the 6-position. It is a selective alpha-adrenergic receptor agonist used to treat urinary incontinence. It exhibits alpha-adrenergic agonist activity. It belongs to the monochlorobenzene, aromatic ether, sulfonamide, and imidazole derivative classes of compounds.
Dabuzalgron (Ro 115-1240) is an orally active and selective α-1A adrenergic receptor agonist developed for the treatment of urinary incontinence. It has a molecular weight of 317.79 and a molecular formula of C12H16ClN3O3S. The compound has a CAS number of 219311-44-1 and a UNII code of LGX4GZ74WO. It protects against doxorubicin-induced cardiotoxicity. It was developed by Hoffman-LaRoche and discontinued in Phase 2 clinical trials. The compound is for research use only and has not been approved for clinical use. |
| Molecular Formula |
C12H16CLN3O3S
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| Molecular Weight |
317.7917
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| Exact Mass |
317.06
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| CAS # |
219311-44-1
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| Related CAS # |
219311-44-1;219311-43-0 (HCl);
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| PubChem CID |
216249
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| Appearance |
White to off-white solid powder
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| Density |
1.46
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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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| Index of Refraction |
1.629
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| LogP |
2.318
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
20
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| Complexity |
463
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FOYWMEJSRSBQGB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H16ClN3O3S/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)
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| Chemical Name |
N-[6-chloro-3-(4,5-dihydro-1H-imidazol-2-ylmethoxy)-2-methylphenyl]methanesulfonamide
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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 : ~26 mg/mL (~81.82 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.55 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 (6.55 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1467 mL | 15.7337 mL | 31.4673 mL | |
| 5 mM | 0.6293 mL | 3.1467 mL | 6.2935 mL | |
| 10 mM | 0.3147 mL | 1.5734 mL | 3.1467 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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