In vitro activity: PF-05089771 is a potent and subtype selective NaV1.7 inhibitor with IC50 of 11 nM. It binds to a site in the voltage sensing domain and interacts with the voltage-sensor domain (VSD) of domain IV. PF-05089771 exhibits a slow onset of block that is depolarization and concentration dependent, with a similarly slow recovery from block. Furthermore, the onset of block by PF-05089771 develops with similar rates using protocols that bias channels into predominantly fast- or slow-inactivated states, suggesting that channel inhibition is less dependent on the availability of a particular inactivated state than the relative time that the channel is depolarized.

Kinase Assay: PF-05089771 is a potent and subtype selective NaV1.7 inhibitor with IC50 of 11 nM. It binds to a site in the voltage sensing domain and interacts with the voltage-sensor domain (VSD) of domain IV.