AM-2099

AM-2099 is a potent and selective inhibitor of voltage-gated sodium channel Nav1.7 with an IC₅₀ of 0.16 μM for human Nav1.7. IC50 & Target: IC50: 0.16 μM (human Nav1.7), 0.18 μM (mouse Nav1.7), 3.5 μM (rat Nav1.7) ^[1] In Vitro: In heterologous cells, comparable inhibition is observed across human, mouse, dog, and cynomolgus monkey NaV1.7 with reduced activity against rat NaV1.7. AM-2099 is more than 100-fold selective over Nav1.3, Nav1.4, Nav1.5, and Nav1.8, while lower levels of selectivity are observed against Nav1.1, Nav1.2, and Nav1.6. AM-2099 demonstrates low affinity for hERG (>30 µM) and does not show greater than 50% inhibition against a panel of 100 kinases (1 µM) and a broad CEREP panel (10 µM). ^[1]. In Vivo: AM-2099 demonstrates a favorable pharmacokinetic profile in rat and dog. In rats AM-2099 shows low total clearance and moderate Vdss and half-life. In contrast, when dosed in dogs AM-2099 shows very low clearance, a low Vdss and long halflife (18 h). AM-2099 demonstrates a dose-dependent increase in plasma exposure with a concomitant dose-dependent reduction in scratching bouts compared to vehicle-treated animals, with a statistically significant reduction observed at the 60 mg/kg dose^[1].