| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
The primary target of Zatebradine HCl is the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel family, comprising HCN1, HCN2, HCN3, and HCN4. It acts as a potent inhibitor of these channels with an IC50 of 1.96 μM for HCN channels. Zatebradine HCl blocks slow inward currents through human HCN1, HCN2, HCN3, and HCN4 channels with IC50 values of 1.83 μM, 2.21 μM, 1.90 μM, and 1.88 μM, respectively. The compound produces use-dependent inhibition of the cardiac pacemaker current. The use-dependent blockade by Zatebradine of the cardiac pacemaker current from rabbit sino-atrial node cells has an apparent Kd of 480 nM. By blocking HCN channels, Zatebradine HCl reduces the pacemaker current, leading to a decrease in heart rate.
|
|---|---|
| ln Vitro |
In rabbit sinoatrial node cells, zatebradine exhibits an apparent Kd of 480 nM for usage-dependent inhibition of cardiac pacemaker currents [2].
In vitro, Zatebradine HCl is a potent inhibitor of HCN channels. It blocks slow inward currents through human HCN1, HCN2, HCN3, and HCN4 channels with IC50 values of 1.83 μM, 2.21 μM, 1.90 μM, and 1.88 μM, respectively. The use-dependent blockade by Zatebradine of the cardiac pacemaker current from rabbit sino-atrial node cells has an apparent Kd of 480 nM. The compound's activity is typically measured using electrophysiological recordings (e.g., patch-clamp) in cells expressing HCN channels. In these assays, Zatebradine HCl is applied to cells, and the amplitude of HCN-mediated currents is measured. |
| 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, Zatebradine HCl is a bradycardic agent that decreases the heartbeat in a reversible manner. It has been extensively studied for its potential therapeutic applications in the treatment of various cardiovascular diseases, such as angina pectoris, heart failure, and arrhythmias. By blocking HCN channels in the sinoatrial node, Zatebradine HCl reduces the pacemaker current, leading to a decrease in heart rate without affecting other cardiovascular parameters. The compound's use-dependent inhibition ensures that its effects are more pronounced at higher heart rates, providing a favorable safety profile. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Zatebradine HCl are not conventional enzyme inhibition studies, as the compound is an ion channel blocker rather than an enzyme inhibitor. Instead, the primary assays involve electrophysiological recordings using patch-clamp or two-electrode voltage clamp techniques in cells expressing HCN1, HCN2, HCN3, or HCN4 channels. In these assays, Zatebradine HCl is applied to cells, and the amplitude of HCN-mediated currents is measured. The IC50 values for each subtype (1.83 μM for HCN1, 2.21 μM for HCN2, 1.90 μM for HCN3, and 1.88 μM for HCN4) are determined from dose-response curves. Radioligand binding studies using channel-specific ligands can also be performed to assess the compound's binding affinity.
|
| Cell Assay |
In vitro cellular assays for Zatebradine HCl are conducted in cells expressing HCN channels, such as HEK293 cells or sinoatrial node cells. Cells are treated with varying concentrations of Zatebradine HCl, and HCN channel activity is assessed using electrophysiological recordings or fluorescent membrane potential dyes. The compound's ability to inhibit HCN-mediated currents is quantified by measuring the decrease in current amplitude. These assays confirm that Zatebradine HCl engages its target in a cellular context and produces the expected inhibition of HCN channel activity.
|
| 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 HCl are conducted in animal models of cardiovascular disease, such as dogs, rabbits, or rats. Animals are administered the compound, and heart rate, blood pressure, and cardiac electrophysiology are monitored using electrocardiography (ECG). The compound's ability to reduce heart rate without affecting other cardiovascular parameters is assessed. These studies confirm that Zatebradine HCl is effective in vivo and provide information about its therapeutic potential for the treatment of angina pectoris, heart failure, and arrhythmias. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Zatebradine HCl indicate that it has a molecular weight of 493.04 and a molecular formula of C26H37ClN2O5. The compound is soluble in DMSO at a concentration of 10 mM, facilitating its use in in vitro assays and formulation for in vivo administration. For storage, the powder should be kept under the recommended conditions in the Certificate of Analysis. The compound's purity is typically high, ensuring quality and reproducibility in experimental studies.
|
| Toxicity/Toxicokinetics |
The toxicological profile of Zatebradine HCl is derived from preclinical and clinical studies. As an HCN channel inhibitor, potential on-target effects include bradycardia, hypotension, and fatigue, which are well-documented class effects of bradycardic agents. The compound's use-dependent inhibition ensures that its effects are more pronounced at higher heart rates, providing a favorable safety profile. Comprehensive toxicology studies would be required for full clinical development, including assessments of cardiovascular, neurological, and hepatic function.
|
| References | |
| Additional Infomation |
Zatebradine HCl is a potent inhibitor of HCN channels. It has an IC50 of 1.96 μM for HCN channels and blocks slow inward currents through human HCN1, HCN2, HCN3, and HCN4 channels with IC50 values of 1.83 μM, 2.21 μM, 1.90 μM, and 1.88 μM, respectively. Zatebradine HCl is a bradycardic agent that decreases the heartbeat in a reversible manner. It has been studied for the treatment of angina pectoris, heart failure, and arrhythmias. Zatebradine HCl is not approved for clinical use and is available from research chemical suppliers for preclinical studies.
|
| Molecular Formula |
C26H37CLN2O5
|
|---|---|
| Molecular Weight |
493.03538
|
| Exact Mass |
492.239
|
| CAS # |
91940-87-3
|
| Related CAS # |
Zatebradine;85175-67-3
|
| PubChem CID |
3045335
|
| Appearance |
Off-white to light yellow solid powder
|
| Density |
1.115g/cm3
|
| Boiling Point |
612.5ºC at 760mmHg
|
| Flash Point |
324.3ºC
|
| LogP |
3.952
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
34
|
| Complexity |
591
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
ZRNKXJHEQKMWCH-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H36N2O5.ClH/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,6,9-14,18H2,1-5H31H
|
| Chemical Name |
3-[3-[2-(3,4-Dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one hydrochloride
|
| Synonyms |
Zatebradine HCl UL-FS49 UL FS49Zatebradine Hydrochloride ULFS49
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
H2O : ~100 mg/mL (~202.82 mM)
DMSO : ~100 mg/mL (~202.82 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.07 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 (5.07 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 (5.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 110 mg/mL (223.11 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0282 mL | 10.1412 mL | 20.2823 mL | |
| 5 mM | 0.4056 mL | 2.0282 mL | 4.0565 mL | |
| 10 mM | 0.2028 mL | 1.0141 mL | 2.0282 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
