GNE-131 is a potent and selective inhibitor of human sodium channel NaV1.7, with an IC50 of 3 nM.
GNE-131 (Compound 13) shows moderate clearance in human liver microsomes and excellent functional activity against human NaV1.7 with an IC50 of 0.003±0.001 μM. GNE-131 shows excellent potency, good in vitro metabolic stability[1].
GNE-131 shows low in vivo clearance in mouse, rat, and dog. GNE-131 also displays excellent efficacy in a transgenic mouse model of induced pain[1].
[1]. Focken T, et al. Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of N-([1,2,4]Triazolo[4,3- a]pyridin-3-yl)methane-sulfonamides as Potent and Selective hNaV1.7 Inhibitors for the Treatment of Pain. J Med Chem. 2018 Jun 14;61(11):4810-4831.