Figure 6.

Potency, selectivity, and state dependence of tool compounds and identified hits. (A) For each Nav1.7 inhibitor, its subtype selectivity against Nav1.2, defined as the ratio of Nav1.2 IC₅₀ value over Nav1.7 IC₅₀ value, was plotted against its Nav1.7 IC₅₀ value. (B) For each Nav1.7 inhibitor, its subtype selectivity against Nav1.5, defined as the ratio of Nav1.5 IC₅₀ value over Nav1.7 IC₅₀ value, was plotted against its Nav1.7 IC₅₀ value. (C) For each Nav1.7 inhibitor, its reciprocal of state dependence was plotted against its potency on Nav1.7. In all three panels, the compounds with desired properties (potent, subtype selective and less state-dependence) distribute to the upper left quadrant.