Na_v1.4 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.

TC-N 1752 is a potent and orally active inhibitor of Nav1.7, with IC₅₀s of 0.17 μM, 0.3 μM, 0.4 μM, 1.1 μM and 2.2 μM at hNav1.7, hNav1.3, hNav1.4, hNaV1.5 and rNav1.8, respectively. TC-N 1752 also inhibits tetrodotoxin-sensitive sodium channels. TC-N 1752 shows analgesic efficacy in the Formalin model of pain.

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

Methocarbamol is an orally active central muscle relaxant and blocks muscular Nav1.4 channel. Methocarbamol reversibly affects voltage dependence of inactivation of Nav1.4 channel. Methocarbamol has the potential for muscle spasms and pain syndromes research.

Nav1.7-IN-23 is an orally active, selective Na_V1.7 inhibitor. Nav1.7-IN-23 exhibits electrophysiological regulatory effects in mouse dorsal root ganglion neurons. Nav1.7-IN-23 can be used for the research of acute pain, chronic inflammatory pain and neuropathic pain.

Huwentoxin-IV TFA is a potent and selective sodium channel blocker, inhibits neuronal Nav1.7, Nav1.2, Nav1.3 and Nav1.4 with IC₅₀s of 26, 150, 338 and 400 nM, respectively. Huwentoxin-IV TFA preferentially blocks peripheral nerve subtype Nav1.7 by binding neurotoxin receptor site 4. Huwentoxin-IV TFA has analgesic effects on animal models of inflammatory and neuropathic pain.

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.

hERG-IN-3 is an orally active hERG blocker with an IC₅₀ of 44.5 nM. hERG-IN-3 exhibits a K_i for β2-adrenergic receptor of 14 nM. hERG-IN-3 exhibits the skeletal muscle Nav1.4 and sodium channel-blocking activities (IC₅₀ = 4.4 μM, 3-fold increasement than hNav1.5). hERG-IN-3 displays a potent antimyotonic activity in an animal model. hERG-IN-3 can be used for the study of Myotonia Congenita.

VGSCs-IN-1 (compound 14), a 2-piperazine analog of Riluzole (HY-B0211), is a human voltage-gated sodium channels (VGSCs) inhibitor. VGSCs-IN-1 shows great Nav1.4 blocking activity. VGSCs-IN-1 has a pKa of 7.6 and a cLog P of 2.4. VGSCs-IN-1 can be used for cell excitability disorders research.

Huwentoxin-IV is a potent and selective sodium channel blocker, inhibits neuronal Nav1.7, Nav1.2, Nav1.3 and Nav1.4 with IC₅₀s of 26, 150, 338 and 400 nM, respectively. Huwentoxin-IV preferentially blocks peripheral nerve subtype Nav1.7 by binding neurotoxin receptor site 4. Huwentoxin-IV has analgesic effects on animal models of inflammatory and neuropathic pain.

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.