Nav1.2-IN-4

Nav1.2-IN-4 (compound 11b) effectively blocks Na_V1.2 channels with an IC₅₀ of 31.21 μM and exhibits a state-dependent mechanism by preferentially inhibiting the inactivated state^[1].
Nav1.2-IN-4 exhibits high passive membrane permeability (6.53 × 10⁻⁶ cm/s)^[1].
Nav1.2-IN-4 exhibits a favorable safety profile with no significant cytotoxicity up to 500 μM in HEK293T and SH-SY5Y cells^[1].
Nav1.2-IN-4 (50 μM) shows low inhibitory activity against cardiac Na_V1.5 channels (12.0% inhibition at 50 μM), indicating a low risk of Na_V1.5-related cardiotoxicity^[1].
Nav1.2-IN-4 exhibits minimal inhibition of major CYP subtypes (CYP3A4, CYP2D6, CYP2C9) at 50 μM^[1].
Nav1.2-IN-4 is predicted to exhibit potent binding affinity for the Na_V1.2 channel with a docking score of -9.1 kcal/mol, forming key hydrogen bonds and π-alkyl interactions within the binding pocket; molecular dynamics simulations from 10-100 ns indicate that this molecule forms a stable, energetically favorable complex with the Na_V1.2 channel, with an MM-GBSA binding free energy of -32.3 kcal/mol, and the binding is primarily driven by van der Waals interactions.

Nav1.2-IN-4 exhibits moderate to weak free radical scavenging activity in ABTS (IC₅₀ = 82.72 μM) and DPPH (IC₅₀ = 510.4 μM) assays^[1].