Acacetin, a Potent Transient Outward Current Blocker, May Be a Novel Therapeutic for KCND3-Encoded Kv4.3 Gain-of-Function-Associated J-Wave Syndromes

Acacetin, a natural flavone, is a potent Ito current blocker. Acacetin may be a novel therapeutic forKCND3-mediated J wave syndrome. KCND3-V392I demonstrated a marked gain-of-function phenotype, increasing peak Itocurrent density by 92.2%. This preclinical study provides pharmacological and functional evidence to suggest that Acacetin may be a novel therapeutic for patients with KCND3 gain-of-function-associated J wave syndrome by inhibiting Itoand abolishing the accentuated action potential notch in patient-derived iPSC-CMs.