AP30663

AP30663 is a novel small molecule inhibitor of the small conductance Ca2+-activated K+ (KCa2, also known as SK) channels, specifically targeting the KCa2.3 subtype. It acts as a negative allosteric modulator by right-shifting the Ca2+-activation curve of these channels[5][6][8]. AP30663 is being developed for the pharmacological conversion of atrial fibrillation (AF) to normal sinus rhythm[1][2][4]. In preclinical and clinical studies, it has been shown to prolong atrial refractoriness with minor effects on other cardiac ion channels and minimal impact on ventricular repolarization[5][6]. Clinical trials have demonstrated that intravenous administration can convert AF to sinus rhythm in a significant proportion of patients without serious adverse events or ventricular arrhythmias; its main side effect is transient QTc interval prolongation and mild infusion site reactions[4][7]. AP30663’s mechanism involves selective inhibition/modulation of KCa2 (SK) channels, which are implicated in atrial repolarization but not significantly involved in ventricular electrophysiology—potentially reducing proarrhythmic risk compared to existing antiarrhythmic drugs. The compound’s development focuses on acute conversion therapy for atrial fibrillation.