NS-1643

Description: NS1643 is a novel and potent human ether-a-go-go related gene (hERG) KV11 channel activator with EC50 of 10.5 uM. In Xenopus laevis oocytes, NS1643 increased both steady-state and tail current at all voltages tested. The EC(50) value for HERG channel activation was 10.5 microM. NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between the ERG1 and ERG2 channels. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well as an increased relative importance for the fast component of deactivation to the total deactivation. In contrast, for ERG1, NS1643 causes a right-ward shift in the voltage-dependent release from inactivation but does not affect time-constants of deactivation.

References: Mol Pharmacol. 2006 Feb; 69(2):658-65. Epub 2005 Nov 11. Mol Pharmacol. 2006 Jan; 69(1):266-77. Epub 2005 Oct 11. Neuropharmacology. 2007 Aug; 53(2):283-94. Epub 2007 May 21.