GS-462808 is a late sodium current inhibitor of the cardiac Nav1.5 channel. GS-462808 had lower brain penetration and serendipitously lower activity at the brain isoforms.
Nav1.7-IN-8 is a highly potent and selective inhibitor of NaV1.7, exhibiting greater selectivity for inhibiting NaV1.7 compared to the subtypes hNaV1.1 and hNaV1.5. Additionally, Nav1.7-IN-8 has inhibitory effects on CYP2C9 and CYP3A4, with IC50 values of 0.17 μM and 0.077 μM, respectively. Notably, Nav1.7-IN-8 demonstrates significant analgesic properties in rodent models of both acute and inflammatory pain.
GDC-0310 is a selective acyl-sulfonamide inhibitor targeting the Na_v1.7 channel, exhibiting a potent inhibitory concentration (IC_50) of 0.6 nM against hNa_v1.7.