PF 05089771 tosylate

Description: PF-05089771 is a voltage-gated sodium channel 1.7 (Nav1.7) blocker (IC50: 11, 16, 33, and 20 nM for 5N11S, 5A11L, 5A11S, and 5A11L Nav1.7 splice variants, respectively). It is selective for Nav1.7 over Nav1.1-1.6 and 1.8 channels (IC50: 0.11-25 µM), L-type calcium, and KvLQT and hERG potassium channels (IC50: >10 µM), as well as human and cynomolgus monkey TRPV1 receptors (IC50: 10/20 µM). PF-05089771 is also 1, 000-fold selective for half-inactivated over resting Nav1.7 channels, and mutation of the domain IV voltage-sensor domain (VSD4) reduces PF-05089771 potency by approximately 100-fold. Target: Sodium Channel. Smiles: CC1=CC=C(C=C1)S(=O)(=O)O.C1=CC(=C(C=C1Cl)C2=C(NN=C2)N)OC3=CC(=C(C=C3Cl)S(=O)(=O)NC4=CSC=N4)F. References: Alexandrou A.J., et al. Subtype-selective small molecule inhibitors reveal a fundamental role for Nav1.7 in nociceptor electrogenesis, axonal conduction and presynaptic release. PLoS One 11(4), e0152405 (2016).