Figure 2. Comparison of NBI-921352 potency on human wild-type Na_V1.6 and patient-identified variants of Na_V1.6.

All constructs were transiently transfected into Expi293F cells and evaluated by automated patch-clamp electrophysiology using the SophionQube. The voltage-clamp methods were identical to those used for evaluation of the wild-type channels. The error bars indicate the 95% confidence interval of the fitted IC₅₀ generated in Prism. The horizontal dotted line is at the IC₅₀ for wild type Na_V1.6 (51 nM, see Figure 1). The gray shaded band indicates the 95% confidence range for the IC₅₀ for wild-type Na_V1.6. Only two variants have fitted IC₅₀’s outside of the 95% confidence interval for the wild-type channel IC₅₀. R850Q was slightly more potently inhibited and R1617Q was less potently inhibited than the wild-type channel. R1617Q is near the proposed binding site for NBI-921352.