molecules of the month

The Xenon NaV1.6 Inhibitor, NBI-921352, is remarkably selective for the NaV1.6 sodium channel over other isoforms (IC50 = 51 nM, 756x vs. NaV1.1, 134X vs. NaV1.2, 276X vs. NaV1.7, >583X vs. 1.3, 1.4, 1.5). The molecule is It is being developed to treat pediatric patients with SCN8A developmental and epileptic encephalopathy (SCN8A-DEE) and other indications such as adult focal epilepsy. The molecule is an arylsulfonamide and has a similar structure to NaV1.7 arylsulfonamide inhibitors, and is a state-dependent inhibitor, preferentially inhibiting activated channels. The molecule was well-tolerated in a Ph. I study at plasma concentrations greater than required for efficacy in preclinical studies, and efficacy will soon be evaluated in Ph. II. NBI-921352 appears to be effective in preventing seizures at…