TABLE 1

Electrophysiologic effects of NS1643 in hERG1 mutations

	V_1/2 Activation		V_0.3 Inactivation		Deactivation		NS1643 ↑ Tail Current
	Baseline	ΔNS1643	Baseline	ΔNS1643	Baseline	ΔNS1643	NS1643 ↑ Tail Current
	mV				ms		%
WT	−22 ± 3	−18 ± 3	−27 ± 3	10 ± 3	216 ± 24	201 ± 74	13 ± 4
Selectivity filter-SF1-EC-1
N629H	−38 ± 5	2 ± 2^*	No inactivation		110 ± 18	21 ± 11^*	−10 ± 7^*
N629T	7 ± 3	−16 ± 5	No inactivation		90 ± 11	53 ± 7	51 ± 18^*
S600C	−19 ± 6	−23 ± 5	−32 ± 9	0 ± 4	106 ± 12	99 ± 15	1 ± 12
Y597V	−28 ± 2	−17 ± 2	−58 ± 3	−2 ± 4^*	147 ± 21	107 ± 34	45 ± 5^*
F627Y	−20 ± 2	−27 ± 4	Inactivation not measured		85 ± 9	98 ± 34	98 ± 34^*
Selectivity filter-SF2-EC-2
K595C	−15 ± 5	−23 ± 7	No inactivation		80 ± 7	50 ± 10	20 ± 11
K610S	−6 ± 2	−20 ± 4	−35 ± 5	4 ± 4	111 ± 27	142 ± 48	7 ± 11
S631A	−2 ± 3	−24 ± 3	29 ± 4	−4 ± 5^*	71 ± 6	102 ± 15	12 ± 4
T613C	−5 ± 1	−23 ± 6	−54 ± 6	−3 ± 3^*	153 ± 16	88 ± 46	−13 ± 10^*
S3S4 linker-EC-1
T436A	−7 ± 4	−21 ± 3	−19 ± 5	−2 ± 4^*	195 ± 28	162 ± 48	12 ± 9
N573Y	−11 ± 6	−15 ± 5	−28 ± 7	10 ± 2	367 ± 118	130 ± 63	37 ± 16^*
N598T	−17 ± 3	−29 ± 3^*	−35 ± 5	11 ± 5	173 ± 34	174 ± 41	−10 ± 9^*
M574A	−14 ± 4	−26 ± 2^*	−23 ± 8	4 ± 7	190 ± 22	186 ± 66	−4 ± 5
S3S4 linker-EC-2
E435A	−20 ± 4	−15 ± 5	−29 ± 4	9 ± 2	239 ± 22	75 ± 26^*	11 ± 14
G522A	−17 ± 4	−21 ± 4	−30 ± 5	11 ± 3	157 ± 18	170 ± 44^*	25 ± 7
S4S5 linker-IC-1
R541D	−22 ± 3	−24 ± 4	−17 ± 5	10 ± 3	84 ± 16	177 ± 51^*	6 ± 6
M651T	−27 ± 2	−27 ± 2	−54 ± 7	15 ± 7	396 ± 86	132 ± 95^*	8 ± 16
M645I	−39 ± 6	−27 ± 4	No inactivation		62 ± 3	91 ± 15^*	165 ± 53^*
Y667D	−23 ± 3	−22 ± 3	−21 ± 3	3 ± 6	17 ± 8	36 ± 21^*	271 ± 51^*
L564A	−21 ± 1	−24 ± 1	4 ± 4	−7 ± 4	232 ± 24	125 ± 32^*	−5 ± 9^*
E544L	−7 ± 3	−24 ± 3	−37 ± 12	29 ± 6^*	31 ± 3	77 ± 14^*	398 ± 79^*
S4S5 linker-IC-2
T526M	−58 ± 4	−59 ± 9^*	−25 ± 15	33 ± 5^*	75 ± 18	201 ± 73^*	48 ± 40
I567A	−3 ± 3	−20 ± 1	−36 ± 5	10 ± 3	123 ± 16	142 ± 57^*	37 ± 10^*

↵* p < 0.05 difference in the drug-induced change seen in the mutation compared with the drug-induced change observed in WT.