Table 1.

Nav inhibitory activity of HNTX-III analogs

Compound	Substitution	hNav1.7 IC50 (μM)	p Values
1	Wildtype	0.211 ± 0.049	-
2	Gly1Phe	0.282 ± 0.056	NS
3	Gly1Lys	0.150 ± 0.024	NS
4	Gly4delete	>10	<0.0001
5	Gly4Gln	0.815 ± 0.031	<0.0001
6	Phe5Trp	1.227 ± 0.167	<0.001
7	Phe5Leu	2.041 ± 0.015	<0.0001
8	Gly6Trp	0.167 ± 0.017	NS
9	Thr10Glu	1.657 ± 0.037	<0.001
10	Pro11Lys	0.127 ± 0.026	<0.01
11	Pro11Glu	0.927 ± 0.076	<0.01
12	Gly12Glu	1.891 ± 0.142	<0.0001
13	Pro18Lys	0.050 ± 0.002	<0.0001
14	Pro18Leu	0.255 ± 0.078	NS
15	Pro18Trp	0.225 ± 0.027	NS
16	Asn19Lys	0.431 ± 0.058	<0.0001
17	Asn19Leu	0.092 ± 0.046	<0.0001
18	Tyr20Trp	0.495 ± 0.039	<0.0001
19	Ala21Leu	0.133 ± 0.010	<0.01
20	Ala21Val	0.099 ± 0.019	<0.0001
21	21Val	0.512 ± 0.078	<0.0001
22	Lys25Arg	0.647 ± 0.046	<0.0001
23	His26Asp	7.58 ± 0.020	<0.0001
24	His26Leu	5.781 ± 0.117	<0.0001
25	His26Lys	>10	<0.0001
26	Lys27Gln	0.568 ± 0.042	<0.0001
27	Lys30Arg	>10	<0.0001
28	Tyr32Leu	3.076 ± 0.054	<0.0001
29	Tyr32Trp	0.075 ± 0.016	<0.0001
30	Leu33Glu	>10	<0.0001
31	Leu33Lys	>10	<0.0001
32	Leu33Phe	0.215 ± 0.029	NS
33	Ala0Gly1	0.486 ± 0.073	<0.0001
34	Lys0Gly1	0.086 ± 0.012	<0.0001
35	Phe0Gly1	0.475 ± 0.091	<0.0001
36	Lys0Leu1	0.145 ± 0.049	NS

Data are shown mean ± SD, n = 3 to 5 cells, one-way ANOVA followed by Dunnett’s post hoc tests.

NS, not significant.