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Chemical Structure| 1262618-39-2 Chemical Structure| 1262618-39-2

Structure of GS967
CAS No.: 1262618-39-2

Chemical Structure| 1262618-39-2

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GS-967 is a selective inhibitor of cardiac late sodium current (late INa ). The IC50 values in ventricular myocytes and isolated hearts are 0.13 μM and 0.21 μM.

Synonyms: GS458967

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Product Details of GS967

CAS No. :1262618-39-2
Formula : C14H7F6N3O
M.W : 347.22
SMILES Code : FC(C1=NN=C2C=CC(C3=CC=C(OC(F)(F)F)C=C3)=CN21)(F)F
Synonyms :
GS458967
MDL No. :MFCD28385879
InChI Key :FEVBKJITJDHASC-UHFFFAOYSA-N
Pubchem ID :58118983

Safety of GS967

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P264-P270-P301+P312-P330

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
ND7/23 cells 1 μM GS967/Prax330 reduced the persistent current of the mutant channel from 6.6% of peak current to 1.1% and caused a 15 mV depolarizing shift in the voltage dependence of channel inactivation. Brain. 2019 Feb 1;142(2):362-375
rabbit ventricular myocytes 1 μmol/l suppressed hypokalemia-induced EADs Circulation. 2015 Oct 20;132(16):1528-1537
Porcine ventricular cardiomyocytes 1 μmol/L Inhibition of I NaL, restoring APD and repolarization stability in ischemic heart failure model. Circ Arrhythm Electrophysiol. 2020 Apr;13(4):e008130
Rabbit ventricular cardiomyocytes 1 μmol/L Inhibition of I NaL, shortening action potential duration (APD), and restoring APD and repolarization stability in heart failure. Circ Arrhythm Electrophysiol. 2020 Apr;13(4):e008130
HCM cardiomyocytes 0.5 μM >3 minutes GS-967 reduced Ca2+-transient amplitude and contractility under β-adrenoceptor stimulation while maintaining the acceleration of relaxation. Br J Pharmacol. 2018 Jul;175(13):2635-2652
HCM cardiomyocytes 0.5 μM >3 minutes GS-967 shortened action potential duration, reduced diastolic [Ca2+], hastened Ca2+ transients and twitch kinetics, and reduced arrhythmogenic early and delayed after-depolarizations. Br J Pharmacol. 2018 Jul;175(13):2635-2652
hippocampal fast-spiking inhibitory interneurons 3 μM GS967 inhibited persistent Na+ currents and reduced action potential frequency. J Clin Invest. 2021 Nov 1;131(21):e142202
iPSC-CMs 1 μM GS967 significantly shortened APD90 in cells carrying the Y1103 allele but had no effect on SS cells Circulation. 2022 Jan 25;145(4):299-308
Xenopus oocytes 5 μM GS967 drastically reduced persistent currents and markedly delayed recovery from inactivation for WT and mutants J Headache Pain. 2019 Nov 15;20(1):107
HEK-293 cells 5 μM GS967 inhibited persistent currents of all SCNA1 FMH3-related mutants and dramatically slowed the recovery from fast inactivation of WT and mutants J Headache Pain. 2019 Nov 15;20(1):107
LQT2 cardiomyocytes 100 nM GS967 accelerated Ca2+ transient decay by accelerating Na+/Ca2+ exchanger (INCX)-mediated Ca2+ efflux, thereby reducing EADs Circ Arrhythm Electrophysiol. 2020 Aug;13(8):e006875
Canine ventricular cardiomyocytes (SR and CAVB models) 100, 300, 1000 nM GS967 concentration-dependently reduced the incidence of dofetilide-induced early afterdepolarizations (EADs). At 1000 nM, EADs remained present in 42% of SR cardiomyocytes and 35% of CAVB cardiomyocytes. Br J Pharmacol. 2018 Jun;175(12):2470-2482
Canine ventricular cardiomyocytes 100, 300, 1000 nM GS967 concentration-dependently shortened action potential duration (APD) and reduced short-term variability (STV) of repolarization. At 1000 nM, GS967 significantly shortened APD and reduced STV. Br J Pharmacol. 2018 Jun;175(12):2470-2482

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rabbit Isolated rabbit heart model Perfusion 1 μmol/l 30 minutes Prevented hypokalemia-induced VT/VF Circulation. 2015 Oct 20;132(16):1528-1537
Mice Scn1aL1649Q knock-in mice Oral 8 mg/kg (chow) and 2 μM (drinking water) Commenced at P14 GS967 significantly prolonged the lifespan of homozygous Scn1aL1649Q knock-in mice. J Clin Invest. 2021 Nov 1;131(21):e142202
Mice Scn8acond/+,EIIa-Cre mouse model Oral 8 mg/kg Continuous administration starting from postnatal day 1 GS967/Prax330 prolonged the survival of Scn8acond/+,EIIa-Cre mice, increasing the average lifespan from 15 days to 21 days. Brain. 2019 Feb 1;142(2):362-375
Transgenic rabbits Transgenic rabbit model of LQT2 Perfusion 30 nM and 100 nM GS967 significantly reduced the incidence of EADs and PVTs by increasing Ca2+ efflux, with minimal effects on APD or CV restitution kinetics under basal conditions Circ Arrhythm Electrophysiol. 2020 Aug;13(8):e006875
Dogs Chronic atrioventricular block (CAVB) model Intravenous 0.1 mg/kg Single dose, administered over 5 min GS967 completely abolished dofetilide-induced Torsades de Pointes (TdP) arrhythmias (10/14 dogs had no TdP after GS967 treatment), while single ectopic beats (sEB) persisted in 9 animals. GS967 significantly reduced spatial dispersion of repolarization. Br J Pharmacol. 2018 Jun;175(12):2470-2482

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.88mL

0.58mL

0.29mL

14.40mL

2.88mL

1.44mL

28.80mL

5.76mL

2.88mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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