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SEA0400 is a **potent and highly selective small molecule inhibitor of the sodium-calcium exchanger (NCX), with the greatest selectivity for the cardiac NCX1 isoform**[3][1]. Its primary mechanism is the **blockade of the forward and reverse modes of NCX-mediated Ca\(^{2+}\) extrusion and influx**[3]. SEA0400 is used in experimental models to study NCX function in isolated cardiac cells, neuronal tissues, and for evaluating the pathophysiological role of NCX in heart conditions, arrhythmia, and potentially other diseases[1][2][3]. Its pharmacological profile includes an IC\(_{50}\) of approximately 27–40 nM for NCX1 inhibition and minimal off-target activity at concentrations ≤1 μM[1][3]. It does not significantly affect sodium, L-type calcium, inwardly rectifying potassium, or delayed rectifier potassium currents at these concentrations, distinguishing it as more selective than older NCX inhibitors like KB-R7943[3]. SEA0400 can alter intracellular Ca\(^{2+}\) dynamics, potentially providing antiarrhythmic effects in settings of NCX upregulation, but may be proarrhythmic or cytotoxic when NCX function is chronically reduced[2]. Developed for research, not approved as a marketed therapeutic agent.
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