LB992 NTX-2009, a novel charged sodium channel blocker has significant anti-inflammatory activity in an atopic dermatitis model and produces sustained inhibition of chloroquine-induced itch

Charged sodium channel blockers (CSCBs) such as NTX-2009 do not cross membranes, and selectively inhibit sensory nerves by gaining access to nociceptors through large pore channels (eg TRPV1, TRPA1) that are open due inflammation. Evidence suggests transmit itch pain signals the CNS play an important role in driving immune response psoriasis atopic dermatitis. We examined whether blockade of skin would have anti-inflammatory activity well anti-pruritic effects models dermatitis (AD). A topical gel formulation was tested for its ability chloroquine (CQ)-induced scratching. Injection CQ produced eight-fold increase scratching duration compared saline injected mice. (0.1 - 1.0%) applied 3 hours before injection dose dependently decreased duration, with 0.3% producing a 73% inhibition 1% complete inhibition. The action characterized >70% reduction maintained out 15 hrs. (0.3% QD) evaluated calcipotriol model AD. Calcipotriol (CP) administered mice once daily 10 days ruxolitinib (10 mM, used positive control. Experimental endpoints were clinical score (erythema, edema desquamation), gene expression histology. significantly reduced greater effect than ruxolitinib. CP increased IL-4 while decreasing Filaggrin-2 expression. Both reversed Dermal thickness mast cell infiltration both inhibited This data demonstrates potential new class CSCBs, NTX-2009.