SAR296968 (SAR 296968) is a potent, selective Na+/Ca2+ exchanger (NCX) inhibitor, potently inhibits hNCX1/2/3 with IC50 of 74/23/129 nM, respectively.
SAR296968 showed the same range of inhibitory potency on NCX1 orthologs from dog, guinea pig, pig, rabbit, and rat (IC50=20-200 nM).
SAR296968 inhibited both the forward and reverse mode of the NCX current in a concentration-dependent manner with similarly high potency in voltage-clamp studies in guinea pig cardiomyocytes.
SAR296968 displays little to no effect against 5-HT2B, benzodiazepine peripheral receptor, norepinephrine uptake, dopamine uptake, AR and PR.
SAR296968 exhibited antiarrhythmic properties in animal models of arrhythmias related to early or late afterdepolarizations, significantly increased left ventricular contractility in anesthetized pigs.
