Table 1. Inhibitory Potencies of the Parent, Precursors, and Bivalent Ligands at hNa_V1.4 and hNa_V1.7^a.

	Ligand	IC50 (nM ± SEM)	IC50 relative to 1	n
hNaV1.4
	Bivalent ligands
1	[m3-HwTx-IV]-[PEG80]-[K-KIIIA]	9 ± 1	1	3
2	[m3-HwTx-IV]-[PEG60]-[K-KIIIA]	14 ± 1	1.6× ↑	3
3	[m3-HwTx-IV]-[PEG120]-[K-KIIIA]	13 ± 3	1.4× ↑	3
	Controls
4	[m3-HwTx-IV]-[PEG40]-[K-KIIIA]	29 ± 5	3.2× ↑	4
5	AzK-KIIIA/S-m3-HwTx-IV	33 ± 8	3.7× ↑	3
6	AzK-KIIIA	32 ± 10	3.6× ↑	3
7	μ-KIIIA30	48 ± 6b	5.3× ↑	3
8	[K-KIIIA]-[PEG80]	144 ± 46	16.0× ↑	4
9	S-m3-HwTx-IV	212 ± 20	23.6× ↑	4
10	m3-HwTx-IV36	369 ± 196c	41.0× ↑	6
11	HwTx-IV49	400 ± nab	44.4× ↑	3
12	[m3-HwTx-IV]-[PEG80]	409 ± 64	45.4× ↑	4
hNaV1.7
	Bivalent ligand
1	[m3-HwTx-IV]-[PEG80]-[K-KIIIA]	6 ± 0.1	1	3
	Controls
4	[m3-HwTx-IV]-[PEG40]-[K-KIIIA]	6 ± 2	no change	4
5	AzK-KIIIA/S-m3-HwTx-IV	6 ± 1	no change	3
6	AzK-KIIIA	96 ± 41	16.0× ↑	3
7	μ-KIIIA	132 ± 37	22.0× ↑	4
9	S-m3-HwTx-IV	4 ± 0.3	1.5x ↓	4
10	m3-HwTx-IV34	0.4 ± 0.1	15.0× ↓	6
11	HwTx-IV34	17 ± 2	2.8× ↑	10
12	[m3-HwTx-IV]-[PEG80]	8 ± 1	1.3× ↑	4

^an is the number of cells, with each cell considered an independent experiment.

^bIC₅₀ values were determined on rat Na_V channel.

^cThe IC₅₀ value was determined for the peptide with no C-terminal amidation. Legend: n.a., not available; ↑, fold increase in IC₅₀ relative to ligand 1; ↓, fold decrease in IC₅₀ relative to ligand 1.