1430806-04-4

PF-05089771 is a voltage-gated sodium channel 1.7 (Na_v1.7) blocker (IC₅₀s = 11, 16, 33, and 20 nM for 5N11S, 5A11L, 5A11S, and 5A11L Na_v1.7 splice variants, respectively). It is selective for Na_v1.7 over Na_v1.1-1.6 and 1.8 channels (IC₅₀s = 0.11-25 μM), L-type calcium, and K_vLQT and hERG potassium channels (IC₅₀s = ≥10 μM), as well as human and cynomolgus monkey TRPV1 receptors (IC₅₀s = 10 and 20 μM, respectively). PF-05089771 is also 1,000-fold selective for half-inactivated over resting Na_v1.7 channels, and mutation of the domain IV voltage-sensor domain (VSD4) reduces PF-05089771 potency by approximately 100-fold.

PF-05089771 is a selective and potent inhibitor of the human voltage-gated sodium ion channel Nav1.7 with an IC50 value of 11 nM. PF-05089771 targets the voltage-sensing domain, preferentially interacting with, and stabilizing, inactivated channel conformations by interaction with the voltage-sensor domain (VSD) of Domain 4. Nav1.7 is expressed in sensory neurons and is critical for pain processing. PF-05089771 is being investigated for the treatment of chronic neuropathic pain.

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