PF-06526290

PF-06526290 is a voltage-gated sodium (Nav) channel modulator with dual activity of enhancing and inhibiting Nav channel conduction. PF-06526290 slows inactivation by binding to the resting state of Nav channels, and exerts inactivation state-dependent inhibition after prolonged depolarization by acting on the voltage sensor of the fourth homologous domain 4 (D4 VSD). PF-06526290 can be used in research on neurological disorders such as epilepsy and autism^[1][2]. In Vitro:PF-06526290 (10 μM; 5 s or sustained depolarization) significantly slowed Nav1.3 current inactivation in HEK293 cells stably transfected with human Nav1.3 (EC₅₀ = 1.1 μM), and exhibited an inhibitory effect on Nav1.3 after prolonged depolarization (IC₅₀ = 5.1 μM)^[1].
PF-06526290 (10 μM; 5 s or sustained depolarization) significantly slowed Nav1.7 current inactivation in HEK293 cells stably transfected with human Nav1.7 (EC₅₀ = 0.27 μM), but lacked inhibitory effects after prolonged depolarization (IC₅₀ > 30 μM)^[1].
PF-06526290 (10 μM; 5 s) slowed current inactivation of these sodium channel subtypes to varying degrees in cells stably transfected with human Nav1.1, Nav1.2, Nav1.4, Nav1.5, Nav1.6, and Nav1.8^[1].
PF-06526290 (10 μM; persistent depolarization) exhibits altered inhibitory potency against the M123 mutation in cells expressing human Nav1.3/Nav1.7 M123 chimeric mutants (the Nav1.3 M123 mutation attenuates inhibition (IC₅₀ = 30 μM), while the Nav1.7 M123 mutation enhances inhibition (IC₅₀ = 35 μM))^[1].
PF-06526290 (10 μM; continuously present) slows the inactivation of TTX-sensitive and TTX-resistant sodium currents in mouse dorsal root ganglion (DRG) neurons^[1].


PF-06526290 (0.3 μM) decreases action potential threshold, initially increases action potential firing frequency, and subsequently prolongs action potential duration in mouse dorsal root ganglion (DRG) neurons^[1].