| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Eleclazine targets the voltage-gated sodium channel (Nav) isoform Nav1.5, which is predominantly expressed in cardiac tissue. It selectively inhibits the late sodium current (late INa) while having minimal effect on the peak sodium current, thereby reducing sodium and calcium overload without disrupting normal cardiac depolarization.
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| ln Vitro |
Eleclazine hydrochloride (also known as GS-6615) is a novel late Na+ current inhibitor with IC50 value of 0.7 uM. Enhanced late Na+ current (late INa ) in the myocardium is pro-arrhythmic. Inhibition of this current is a promising strategy to stabilize ventricular repolarization and suppress arrhythmias. Eleclazine was a selective inhibitor of late INa , stabilizes the ventricular repolarization and suppresses arrhythmias in a model of LQT3. The concentrations at which the electrophysiological effects of Eleclazine were observed are comparable to plasma levels associated with QTc shortening in patients with LQT3, indicating that these effects are clinically relevant.
Kinase Assay: Eleclazine is currently in clinical development for the treatment of long QT syndrome 3 (LQT3). Eleclazine hydrochloride inhibits ATX-II enhanced late INa in ventricular myocytes, shorten the ATX-II induced prolongation of APD, MAPD, QT interval, and decreased spatiotemporal dispersion of repolarization and ventricular arrhythmias. Inhibition by GS-6615 of ATX-II enhanced late INa is strongly correlated with shortening of myocyte APD and isolated heart MAPD Cell Assay: GS-6615 inhibited ATX-II enhanced late INa in ventricular myocytes (IC50 = 0.7 μM), shortened the ATX-II induced prolongation of APD, MAPD, QT interval, and decreased spatiotemporal dispersion of repolarization and ventricular arrhythmias. Inhibition by GS-6615 of ATX-II enhanced late INa was strongly correlated with shortening of myocyte APD and isolated heart MAPD (R2 = 0.94 and 0.98 respectively). In contrast to flecainide, GS-6615 had the minimal effects on peak INa . GS-6615 did not decrease the maximal upstroke velocity of the action potential (Vmax) nor widen QRS intervals. Eleclazine inhibits late INa in HEK293 cells expressing the α subunit of Nav1.5 with an IC50 of 0.88 µM. Other reports indicate an IC50 value of approximately 0.7 µM. The compound is a selective inhibitor of late INa and stabilizes ventricular repolarization while suppressing arrhythmias in models of long QT syndrome type 3 (LQT3). |
| ln Vivo |
In vivo, Eleclazine suppresses arrhythmias and stabilizes ventricular repolarization in animal models of LQT3. It has been evaluated in clinical trials for the treatment of LQT2 syndrome, long QT syndrome, ischemic heart disease, ventricular arrhythmia, and long QT syndrome type 3. The compound shows potential for treating various cardiac arrhythmias.
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| Enzyme Assay |
Cell-free assays for Eleclazine typically utilize purified Nav1.5 channels reconstituted into lipid bilayers or liposomes. Channel activity is measured using voltage-clamp or patch-clamp electrophysiology. The compound is applied at varying concentrations, and inhibition of late sodium current is measured as reduced current amplitude during the plateau phase of the action potential. IC50 values are determined from concentration-response curves.
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| Cell Assay |
HEK293 cells expressing the α subunit of the voltage-gated sodium channel Nav1.5 are cultured and subjected to whole-cell patch-clamp electrophysiology. Late sodium current is elicited by depolarizing voltage steps, and the effect of Eleclazine (applied at various concentrations) on late INa amplitude is measured. The compound's selectivity for late versus peak INa is assessed by comparing inhibition of the two current components.
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| Animal Protocol |
In vivo animal studies for Eleclazine are typically conducted in rodent or rabbit models of LQT3 or acquired long QT syndrome. The compound is administered via oral or intravenous routes. Electrocardiographic parameters (QT interval, QT dispersion) are monitored. Arrhythmia induction is assessed, and the compound's ability to suppress arrhythmias and normalize repolarization is evaluated. Pharmacodynamic effects are correlated with plasma drug concentrations.
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| ADME/Pharmacokinetics |
Eleclazine is orally bioavailable. Following oral administration, the compound is absorbed and distributed to cardiac tissue where it exerts its inhibitory effect on late INa. Detailed PK parameters (Tmax, half-life, clearance, volume of distribution) have been characterized in preclinical species and in human clinical trials. The compound is metabolized primarily via hepatic pathways, with elimination occurring through renal and biliary routes.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have evaluated Eleclazine for safety pharmacology endpoints including hERG channel inhibition and cardiovascular safety. The compound's selective inhibition of late INa (rather than peak INa) is designed to minimize proarrhythmic risk. Standard genotoxicity, reproductive toxicity, and chronic toxicity studies have been conducted to support clinical development.
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| References |
Br J Pharmacol.2016 Nov;173(21):3088-3098;Heart Rhythm.2016 Sep;13(9):1860-7.
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| Additional Infomation |
Eleclazine has been used in multiple studies, including the treatment of LQT2 syndrome, long QT syndrome, ischemic heart disease, ventricular arrhythmias, and type 3 long QT syndrome.
Drug Indications Treatment of hypertrophic cardiomyopathy Treatment of congenital long QT syndrome Eleclazine (molecular formula C21H16F3N3O3) was developed by Gilead Sciences as a novel late sodium current inhibitor for the treatment of cardiac arrhythmias. It has been investigated in clinical trials for various indications including LQT2 syndrome, long QT syndrome, ischemic heart disease, ventricular arrhythmia, and LQT3. The compound represents a promising therapeutic strategy for reducing arrhythmic risk in patients with sodium channelopathies and ischemic heart disease. |
| Molecular Formula |
C21H16F3N3O3
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| Molecular Weight |
415.37
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| Exact Mass |
415.114
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| Elemental Analysis |
C, 60.72; H, 3.88; F, 13.72; N, 10.12; O, 11.56
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| CAS # |
1443211-72-0
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| Related CAS # |
1443211-72-0;1448754-43-5 (HCl);
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| PubChem CID |
71183216
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| Appearance |
Solid powder
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| LogP |
4.014
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
578
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(OC1C=CC(=CC=1)C1C=CC2=C(C=1)C(N(CC1N=CC=CN=1)CCO2)=O)(F)F
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| InChi Key |
YNUAEEJQYHYLMS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H16F3N3O3/c22-21(23,24)30-16-5-2-14(3-6-16)15-4-7-18-17(12-15)20(28)27(10-11-29-18)13-19-25-8-1-9-26-19/h1-9,12H,10-11,13H2
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| Chemical Name |
4-(pyrimidin-2-ylmethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1,4-benzoxazepin-5-one
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| Synonyms |
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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 |
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| 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) |
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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 | 2.4075 mL | 12.0375 mL | 24.0749 mL | |
| 5 mM | 0.4815 mL | 2.4075 mL | 4.8150 mL | |
| 10 mM | 0.2407 mL | 1.2037 mL | 2.4075 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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