Na_v1.1 Inhibitor

ICA-121431 is a nanomolar potent and broad-spectrum voltage-gated sodium channel (Na_v) blocker, shows equipotent selectivity for human Na_v1.1 and Na_v1.3 subtypes with IC₅₀ values of 13 nM and 23 nM, respectively. ICA-121431 shows less potent inhibition of Na_v1.2 (IC₅₀=240 nM) and 1,000 fold selectivity against Na_v1.4, Na_v1.6, and the TTX-resistant human Na_v1.5 and Na_v1.8 channels (IC₅₀s >10 μM).

PF-06456384 trihydrochloride is an extremely potent and selective Na_v1.7 sodium channel blocker (IC₅₀: 0.01 nM for hNaV1.7; 75 nM for rNaV1.7; <0.1 nM for mNaV1.7). PF-06456384 trihydrochloride shows no significant analgesic efficacy in the mouse Formalin pain model.

GDC-0310 is a selective acyl-sulfonamide Na_v1.7 inhibitor, with an IC₅₀ of 0.6 nM for hNa_v1.7.

AA43279 is an in gamma-aminobutyric acid (GABA) fast-firing interneurons located activator for Nav1.1 channel (SCN1A) with an EC₅₀ of 9.5 μM. AA43279 enhances specific neuronal firing activity in vitro, and exhibits anticonvulsant activity in rat MEST model.

Phrixotoxin 3 is a potent blocker of voltage-gated sodium channels, with IC₅₀s of 0.6, 42, 72, 288, 610 nM for NaV1.2, NaV1.3, NaV1.4, NaV1.1 and NaV1.5, respectively. Phrixotoxin 3 modulates voltage-gated sodium channels with properties similar to those of typical gating-modifier toxins, both by causing a depolarizing shift in gating kinetics and by blocking the inward component of the sodium current.

Ceratotoxin-1 (CcoTx1), a peptide toxin, is an voltage-gated sodium channel subtypes inhibitor. Ceratotoxin-1 inhibits Nav1.1/β1, Nav1.2/β1, Nav1.4/β1, and Nav1.5/β1 with IC₅₀ of 523 nM, 3 nM, 888 nM, and 323 nM, respectively. Ceratotoxin-1 also inhibits Nav1.8/β1.