| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Zatebradine targets hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, specifically HCN1, HCN2, HCN3, and HCN4. It acts as a channel blocker or antagonist of these channels. The compound inhibits the hyperpolarization-activated inward current (If) in sinoatrial node cells. Zatebradine exhibits IC50 values of 1.83 microM, 2.21 microM, 1.90 microM, and 1.88 microM for HCN1, HCN2, HCN3, and HCN4, respectively. The overall IC50 for HCN channels is approximately 1.96 microM. The compound also shows activity at dopamine receptors.
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| ln Vitro |
When it comes to usage-dependently blocking cardiac pacemaker currents from rabbit sinoatrial node cells, zebradine has an apparent Kd of 480 nM [2].
In vitro studies have characterized Zatebradine as a potent inhibitor of HCN channels. It blocks the slow inward current through human HCN1, HCN2, HCN3, and HCN4 channels with IC50 values of 1.83 microM, 2.21 microM, 1.90 microM, and 1.88 microM, respectively. The use-dependent blockade of the cardiac pacemaker current from rabbit sino-atrial node cells has an apparent Kd of 480 nM. At 10 microM, the compound achieves 92% inhibition of the hHCN1-mediated current. The compound's activity is characterized by its ability to decrease heartbeat in a reversible manner. |
| ln Vivo |
Zatebradine (0–20 mg/kg; intraperitoneally; 30 min; male C57/Bl6 mice) increased cardiac arrhythmias and dose-dependently decreased heart rate from 600 to 200 bpm (ED50 = 1.8 mg/kg) [1].
In vivo studies have demonstrated that Zatebradine (0-20 mg/kg; intraperitoneal injection; for 30 minutes) decreases heartbeat in a reversible manner. The compound acts as a bradycardic agent, reducing heart rate by blocking HCN channels in the sinoatrial node. In postsynaptic CA1 pyramidal cells, the compound modulates HCN channel activity. The compound's in vivo effects are consistent with its mechanism as an HCN channel antagonist. Studies have been conducted in various animal models to evaluate its heart rate-reducing effects and electrophysiological properties. |
| Enzyme Assay |
The in vitro assay for Zatebradine involves patch-clamp electrophysiology using cells expressing human HCN channels (HCN1, HCN2, HCN3, HCN4). HEK293 cells or other suitable expression systems are transfected with HCN channel cDNAs. Whole-cell patch-clamp recordings are performed to measure HCN channel currents. Cells are held at a holding potential, and hyperpolarizing voltage steps are applied to activate HCN channels. Zatebradine is applied at various concentrations, and the inhibition of current is measured. IC50 values are determined from dose-response curves. Data analysis using nonlinear regression yields inhibition constants.
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| Cell Assay |
In vitro cellular assays for Zatebradine are conducted using cell lines expressing HCN channels, such as HEK293 cells transfected with HCN1, HCN2, HCN3, or HCN4 cDNAs. Cells are plated on coverslips and used for patch-clamp electrophysiology recordings. Alternatively, fluorescence-based membrane potential assays can be used to measure HCN channel activity. Cells are treated with varying concentrations of Zatebradine, and channel activity is measured. The IC50 values for each HCN subtype are determined. Control experiments include application of vehicle and known HCN channel modulators to validate the assay system.
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| Animal Protocol |
Animal/Disease Models: Male C57/Bl6-mouse[1]
Doses: 0mg/kg, 0.1mg/kg, 1mg/kg, 10mg/kg, 20mg/kg Route of Administration: intraperitoneal (ip) injection; 30 minutes Experimental Results: Acute blood glucose was observed diminished, dose-dependent reductions in glycated hemoglobin Dramatically prevented the reduction in IRI levels at the 3 and 10 mg/kg doses, with no differences in food intake or body weight. In vivo animal studies for Zatebradine are typically performed in rodents or rabbits. The compound is administered via intraperitoneal injection at doses ranging from 0-20 mg/kg. Heart rate is monitored using electrocardiography (ECG) or telemetry. The compound's bradycardic effect is assessed by measuring the reduction in heart rate over time. Electrophysiological recordings from sinoatrial node cells can be performed ex vivo to evaluate the compound's effects on pacemaker currents. Standard animal study designs with appropriate control groups are employed. Blood samples are collected for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Zatebradine indicate that it is a potent HCN channel antagonist with a molecular weight of 456.57 g/mol. The compound has a molecular formula of C26H36N2O5. Specific pharmacokinetic parameters such as half-life, bioavailability, and clearance are not extensively reported in the available literature. The compound is formulated for research applications and is typically dissolved in suitable solvents for in vitro and in vivo studies. For in vivo administration, intraperitoneal injection is commonly used. The compound's distribution and metabolism would be consistent with small molecule HCN channel blockers.
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| Toxicity/Toxicokinetics |
Toxicology data for Zatebradine are not extensively reported in the available literature. As an HCN channel blocker, the compound's primary pharmacological effect is heart rate reduction. The main safety concern would be excessive bradycardia or cardiac arrhythmias. Standard toxicity assessments would include evaluation of cardiovascular effects, acute toxicity, and safety pharmacology studies. However, specific toxicity data, including LD50 values and organ toxicity profiles, are not readily available. The compound is for research use only and is not approved for therapeutic applications.
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| References | |
| Additional Infomation |
3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzozazepine-4-one is a benzozazepine.
Zatebradine (UL-FS-49; UL-FS-49CL) is a potent inhibitor of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with an IC50 of 1.96 microM. It blocks HCN1, HCN2, HCN3, and HCN4 with IC50 values of 1.83 microM, 2.21 microM, 1.90 microM, and 1.88 microM, respectively. The compound is a specific bradycardic agent that decreases heartbeat in a reversible manner. It has a molecular formula of C26H36N2O5 and a molecular weight of 456.57 g/mol. Zatebradine is used as a research tool for studying cardiac pacemaker currents and HCN channel biology. |
| Molecular Formula |
C26H36N2O5
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| Molecular Weight |
456.574447631836
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| Exact Mass |
456.262
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| CAS # |
85175-67-3
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| Related CAS # |
Zatebradine hydrochloride;91940-87-3
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| PubChem CID |
65637
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.115g/cm3
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| Boiling Point |
612.5ºC at 760 mmHg
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| Flash Point |
324.3ºC
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| Index of Refraction |
1.545
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
33
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| Complexity |
591
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1CC2C(=CC(=C(C=2)OC)OC)CCN1CCCN(CCC1C=C(OC)C(OC)=CC=1)C
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| InChi Key |
KEDQCFRVSHYKLR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H36N2O5/c1-27(13-9-19-7-8-22(30-2)23(15-19)31-3)11-6-12-28-14-10-20-16-24(32-4)25(33-5)17-21(20)18-26(28)29/h7-8,15-17H,6,9-14,18H2,1-5H3
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| Chemical Name |
3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one
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| Synonyms |
UL-FS-49 free base UL-FS-49CL free baseUL-FS49 UL FS49 ULFS49
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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) |
Ethanol : ~100 mg/mL (~219.02 mM)
DMSO : ≥ 50 mg/mL (~109.51 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.48 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 (5.48 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 (5.48 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 | 2.1902 mL | 10.9512 mL | 21.9024 mL | |
| 5 mM | 0.4380 mL | 2.1902 mL | 4.3805 mL | |
| 10 mM | 0.2190 mL | 1.0951 mL | 2.1902 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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