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Purity: ≥98%
GS967 (also known as GS-458967) is a novel, potent, and selective sodium channel inhibitor exhibiting potent antiarrhythmic effects in various in vitro and in vivo models. It inhibit cardiac late sodium current (late INa ) with IC50 values of 0.13 and 0.21 μM for ventricular myocytes and isolated hearts, respectively. The antiarrhythmic mechanism of GS967 has been attributed to preferential suppression of late sodium current. GS967 (10, 100, 300 nM) completely attenuates the effect of ATX-II (10 nM) to increase action potential duration (APD) and APD variability in ventricular myocytes, with an apparent IC50 value of ∼10 nM and decreased the beat-to-beat variability of APD. GS967 selectively suppressed late I(Na) and prevented and/or reduced the incidence of experimentally induced arrhythmias in rabbit myocytes and hearts.
| ln Vitro |
The effects of ATX-II (10 nM) on increasing action potential duration (APD) and APD variability in ventricular myocytes are completely attenuated by GS967 (10, 100, and 300 nM), with an apparent IC50 value of ~10 nM. It also reduces the step-by-step variability of APD sex[1].
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| ln Vivo |
The proarrhythmogenic effects of the IKr inhibitor E-4031 and the INa late enhancer ATX-II are inhibited and reversed by GS967. GS967 inhibits ischemia-induced arrhythmias and considerably reduces the arrhythmogenic effects of methoxamine-chlorfenium [1]. Usage-dependent blockade (UDB) is consistent with GS967's frequency-dependent reduction of INaP. Compared to ranolazine (16 μM) and lidocaine (17 μM) (IC50=0.07 μM), GS967 induces INaP UDB more potently. Research has shown that GS967 affects the classic long QT syndrome mutation (delKPQ) in the same way [2]. GS967 inhibits the increases in left atrial and left ventricular alternans that are brought on by ischemia. GS967 decreases the increases in repolarization and depolarization heterogeneity brought on by ischemia. GS967 slightly reduces contractility during ischemia, consistent with late INa inhibition, but does not change heart rate, arterial blood pressure, PR and QT intervals, or QRS duration [3].
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| References |
[1]. Belardinelli L, et al. A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias. J Pharmacol Exp Ther. 2013 Jan;344(1):23-32.
[2]. Wei X, et al. Pre- and Delayed Treatments With Ranolazine Ameliorate Ventricular Arrhythmias and Nav1.5 Downregulation in Ischemic/Reperfused Rat Hearts. J Cardiovasc Pharmacol. 2016 Oct;68(4):269-279. [3]. Potet F, et al. Use-Dependent Block of Human Cardiac Sodium Channels by GS967. Mol Pharmacol. 2016 Jul;90(1):52-60. [4]. Bonatti R, et al. Selective late sodium current blockade with GS-458967 markedly reduces ischemia-induced atrial and ventricular repolarization alternans and ECG heterogeneity. Heart Rhythm. 2014 Oct;11(10):1827-35 |
| Molecular Formula |
C14H7F6N3O
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| Molecular Weight |
347.22
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| CAS # |
1262618-39-2
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| SMILES |
FC(C1=NN=C2C=CC(C3=CC=C(OC(F)(F)F)C=C3)=CN21)(F)F
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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) |
Solubility in Formulation 1: 2.5 mg/mL (7.20 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (7.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8800 mL | 14.4001 mL | 28.8002 mL | |
| 5 mM | 0.5760 mL | 2.8800 mL | 5.7600 mL | |
| 10 mM | 0.2880 mL | 1.4400 mL | 2.8800 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.
 GS967 selectively inhibits NaV1.5INaL.Mol Pharmacol.2016 Jul;90(1):52-60. |
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 Concentration dependence of NaV1.5 onset of slow inactivation by GS967, ranolazine, and lidocaine.Mol Pharmacol.2016 Jul;90(1):52-60. |
 GS967 affects NaV1.5-F1760A onset of slow inactivation and recovery from inactivation.Mol Pharmacol.2016 Jul;90(1):52-60. |
 se-dependent block of human NaV1.5 by GS967.
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 GS967 modifies NaV1.5 onset of and recovery from inactivation. Use-dependent block of NaV1.5-F1760A by GS967.Mol Pharmacol.2016 Jul;90(1):52-60. |
 GS967 selectively inhibits NaV1.5-F1760AINaL.Mol Pharmacol.2016 Jul;90(1):52-60. |
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COA
Concentration dependence of NaV1.5 use-dependent block by GS967, ranolazine, and lidocaine.