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10mg |
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25mg |
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50mg |
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Zamicastat is a potent and selective dopamine β-mono-oxygenase inhibitor. Zamicastat Prevents the Deterioration of Cardiometabolic and Inflammatory Biomarkers in a Genetic Model of Salt-sensitive Hypertension. Chronic high salt intake deteriorates several cardiometabolic and inflammatory biomarkers in Dahl/SS rats, which can be prevented by dopamine β-hydroxylase inhibition with zamicastat.
ln Vitro |
After 4 hours of incubation (5, 10, 20, 50, 80, 100 μM), a significant reduction of cell viability was confirmed with 100 μM Zamicastat (p=0.010) in MDCK-BCRP cells. After 4 hours of incubation, no appreciable reduction of cell viability was seen for other doses in any of the cell lines. At 100 μM concentration, no significant loss of cell viability was seen in any of the cell lines when the incubation period was shortened to 30 minutes (p>0.05)[1].
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ln Vivo |
Acute testing of zamicastat (10, 30, and 100 mg/kg/day; oral bolus, 7 days) against salt-induced hypertension in Dahl SS rats was conducted. Blood pressure decreases in a dose-dependent manner when using zamicastat. Following zamicastat administration, the mean 24-hour systolic blood pressure (SBP) decreased by -12.6±4.1 mm Hg (P=0.0284), -15.2±2.7 mm Hg (P=0.0026), and -19.0±3.7 mm Hg (P =0.0036) for dosages of 10, 30, and 100 mg/kg body weight, respectively. A noteworthy decrease in diastolic blood pressure (DBP) of -14.6±3.4 mm Hg (P=0.0073) and -13.0±4.5 mm Hg at the 10 mg/kg body weight dose (P=0.0347) at the 30 mg/kg body weight dose and -15.0±3.1 mm Hg at the 100 mg/kg body weight dose (P=0.0046) was also observed upon zamicastat administration. The administration of zamicastat led to mean arterial pressure (MAP) decreases of -20.6±3.7 mm Hg at 24 hours post-dose, -14.0±3.5 mm Hg (P=0.0101), and -13.4±3.8 mm Hg (P=0.0162). (P=0.0026) at the doses of 10, 30, and 100 mg/kg body weight, in that order. For all tested dosages of zamicastat (10 mg/kg: -19.1±3.2 beats/min, P=0.0019; 30 mg/kg: -13.0±4.5 times/min, P=0.0347; 100 mg/kg: -21.6±6.6 times/min, P=0.0235), there was a slight but significant effect on mean heart rate (HR) 24 hours after dosing.
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Cell Assay |
Cell Viability Assay[1]
Cell Types: MDCK II, MDCK-MDR1 and MDCK-BCRP Cell Tested Concentrations: 5, 10, 20, 50, 80, 100 μM Incubation Duration: 4 hrs (hours) (5, 10, 20, 50, 80, 100 μM) or 30 minutes (100 μM only) Experimental Results: In MDCK-BCRP cells, 100 μM demonstrated a significant loss of cell viability. |
Animal Protocol |
Animal/Disease Models: Sixweeks old male inbred male Dahl SS rat [2]
Doses: 10, 30 or 100 mg/kg; 4 mL/kg Route of Administration: Oral bolus, daily, 7 days Experimental Results: Treatment was dose-dependent Blood pressure drops. Twenty-four hrs (hrs (hours)) after administration, the mean systolic blood pressure decreases on days 10, 30, and 30 were -12.6±4.1 mmHg (P=0.0284), -15.2±2.7 mmHg (P=0.0026), and -19.0±3.7 mmHg. column (P=0.0036). and 100 mg/kg body weight dose respectively. Animal/Disease Models: Tenweeks old male Wistar Han rats [2] Doses: 30 mg/kg/day Route of Administration: Daily in animal feed (mixed into rodent food) Experimental Results: Caused significant levels of norepinephrine excretion in the body Dramatically diminished urine flow by 51% |
References |
[1]. Bicker J, et al. In vitro assessment of the interactions of dopamine β-hydroxylase inhibitors with human P-glycoprotein and Breast Cancer Resistance Protein. Eur J Pharm Sci. 2018 May 30;117:35-40.
[2]. Igreja B, et al. Effects of Zamicastat treatment in a genetic model of salt-sensitive hypertension and heart failure. Eur J Pharmacol. 2019 Jan 5;842:125-132. |
Molecular Formula |
C21H21F2N3OS
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Molecular Weight |
401.4758
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CAS # |
1080028-80-3
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Related CAS # |
1080028-80-3;1383828-47-4 (HCl);
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SMILES |
InChI=1S/C21H21F2N3OS/c22-16-8-15-9-18(13-27-20(15)19(23)10-16)26-17(12-25-21(26)28)6-7-24-11-14-4-2-1-3-5-14/h1-5,8,10,12,18,24H,6-7,9,11,13H2,(H,25,28)/t18-/m1/s1
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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 : ~150 mg/mL (~373.63 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.23 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 (6.23 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.23 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 | 2.4908 mL | 12.4539 mL | 24.9078 mL | |
5 mM | 0.4982 mL | 2.4908 mL | 4.9816 mL | |
10 mM | 0.2491 mL | 1.2454 mL | 2.4908 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.