Nav1.7-IN-8

Nav1.7-IN-8 is a potent blockage of NaV1.7 with high selectivity for the inhibition of NaV1.7 over the subtypes hNaV1.1 and hNaV1.5. Nav1.7-IN-8 inhibits CYP2C9 and CYP3A4 with an IC50 of 0.17 μM and 0.077 μM, respectively. Nav1.7-IN-8 displays significant analgesic effects in rodent models of acute and inflammatory pain[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

Research Areas >> Inflammation/Immunology

CYP2C9:0.17 μM (IC50)

CYP3A4:0.077 μM (IC50)

Nav1.7-IN-8 plasma protein binding is very high in rat with a free fraction of ∼1.1 %[1].

Nav1.7-IN-8 (0~100 mpk, i.p.; 1 hour) shows a reduction of the pain response in phase 2a of the formalin assay in a dose dependent manner and produces a substantial inhibition of the pain response[1]. .Nav1.7-IN-8 (10~100 mpk, i.p.; 2 days) displays a dose-dependent reduction of the pain response[1]. Animal Model: Rats[1] Dosage: 0~100 mpk Administration: I.p.; 1 hour Result: Showed a reduction of the pain response in phase 2a of the formalin assay in a dose dependent manner and produced a substantial inhibition of the pain response. Animal Model: Mice[1] Dosage: 10~100 mpk Administration: I.p.; 2 days Result: Displayed a dose-dependent reduction of the pain response.

[1]. Focken T, et al. Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models. ACS Med Chem Lett. 2016;7(3):277-282. Published 2016 Jan 19.