NS8593

NS8593 is a potent and selective small molecule inhibitor of small conductance Ca2+-activated K+ channels (SK channels; also known as KCa2.1–KCa2.3 or SK1–SK3). It acts as a negative gating modulator by interacting with the channel's inner pore vestibule at a site distinct from the apamin binding site. NS8593 reversibly inhibits SK channel-mediated currents in a Ca2+-dependent manner and can access its high-affinity binding sites from both sides of the cell membrane[1][4][10]. In addition to its primary action on SK channels, NS8593 has been shown to inhibit transient receptor potential melastatin 7 (TRPM7) channels at higher concentrations[5][10]. Preclinical studies indicate that it prolongs atrial effective refractory period without affecting ventricular repolarization or QT interval and demonstrates antiarrhythmic effects in animal models of atrial fibrillation[6][9]. It has also been investigated for its ability to inhibit chondrocyte ferroptosis via TRPM7/HO-1 pathway in models of rheumatoid arthritis[5].

Other names

(R)-N-(Benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine