| Identification | Back Directory | [Name]
GS967 | [CAS]
1262618-39-2 | [Synonyms]
GS967
CS-1742
GS458967
GS-458967
GS 458967
GS967, >98%
GS967(GS-458967)
GS-967;GS 967;GS-458967; GS 458967; GS458967
6-(4-(trifluoroMethoxy)phenyl)-3-(trifluoroMethyl)-[1,2,4]triazolo[4,3-a]pyridine
1,2,4-Triazolo[4,3-a]pyridine, 6-[4-(trifluoromethoxy)phenyl]-3-(trifluoromethyl)- | [Molecular Formula]
C14H7F6N3O | [MDL Number]
MFCD28385879 | [MOL File]
1262618-39-2.mol | [Molecular Weight]
347.22 |
| Chemical Properties | Back Directory | [density ]
1.52±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in H2O; ≥13.35 mg/mL in DMSO; ≥25.52 mg/mL in EtOH with ultrasonic | [form ]
solid | [pka]
-0.41±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
GS967, also known as GS-458967, is a highly selective late sodium channel current blocker. The selective inhibition of late INa with GS967 can exert antiarrhythmic effects by suppressing EAD- and DAD-mediated extrasystolic activity in PFs and PV and SVC sleeve preparations. Selective late INa inhibition with GS967 exerts potent protective effects against ischemia-induced depolarization and repolarization abnormalities in both atria and ventricles. | [Biological Activity]
gs967 is a potent, selective and novel inhibitor of cardiac late sodium current (late ina) with ic50=0.13 μm in ventricular myocytes and ic50=0.21μm in isolated hearts. [1]when na+ channels in myocytes fail to inactivate after opening, na+ influx continues throughout the ap plateau. the resulting na+ current (ina) is referred to as late ina. its magnitude is increased in many pathologic conditions, such as in the failing and/or ischemic heart, in the heart exposed to oxidative stress, and in hearts of patients with congenital long qt3 syndromes. [1]in rabbit isolated ventricular myocytes, inhibition of peak ina by gs967 is in a concentration- and voltage-dependent manner with minimal use-dependent, it also decreases the na+ and ca2+ overload. in rabbit-isolated heart, gs967 abolishes tdp induced by atx-ii or e-4031. [1]in anesthetized rabbit, gs967 reduces mapd90 but did not alter cardiac conduction time; it also prevents the induction of arrhythmic activity and tdp by clofilium and decreases the incidence of ischemia-induced arrhythmias. [1] | [in vivo]
GS967 prevents and reverses proarrhythmic effects of the late INa enhancer ATX-II and the IKr inhibitor E-4031. GS967 significantly attenuates the proarrhythmic effects of methoxamine 1 clofilium and suppressed ischemia-induced arrhythmias[1]. GS967 causes a reduction of INaP in a frequency-dependent manner, consistent with use-dependent block (UDB). GS967 evokes more potent UDB of INaP (IC50=0.07 μM) than ranolazine (16 μM) and lidocaine (17 μM). GS967 is found to exert these same effects on a prototypical long QT syndromemutation (delKPQ)[2]. GS967 prevents ischemia-induced increases in alternans in the left atrium and left ventricle. GS967 reduces ischemia-induced increases in depolarization heterogeneity and repolarizationheterogeneity. GS967 does not alter heart rate, arterial blood pressure, PR and QT intervals, or QRS duration, but it mildly decreased contractility during ischemia, which was consistent with late INa inhibition[3]. | [References]
1. belardinelli l, liu g, smith-maxwell c et al. a novel, potent, and selective inhibitor ofcardiac late sodium current suppresses experimental arrhythmias. j pharmacol exp ther. 2013 jan;344(1):23-32. |
|
|