NS-1643 is a potent human ether-a-go-go related gene (hERG) KV11.1 channel activator with EC50 of 10.5 μM.
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NS1643 is a partial agonist of human ether-a-go-go-related gene (hERG) K(+) channels with an EC50 of 10.5 μM. NS1643 has distinct effects on erg2 (Kv11.2) currents by reducing channel inactivation especially at high concentrations[3]. When assessed with 2-s depolarizations, NS1643 enhanced the magnitude of wild-type hERG (human ether-a-go-go-related gene) current in a concentration- and voltage-dependent manner with an EC(50) of 10.4 mM at -10 mV. NS1643 shifted the voltage dependence of inactivation by +21 mV at 10 mM and +35 mV at 30 mM, but it did not alter the voltage dependence of activation of hERG channels. The agonist activity of NS1643 was facilitated by mutations (F656 to Val, Met, or Thr) that are known to greatly attenuate channel inhibition by hERG blockers[4].
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