nav1.2

Nav1.2-IN-1 (compound 5i) is a 3-(1,2,3,6-tetrahydropyridine)-4-azaindole derivative that acts as a potent and selective Nav1.2 inhibitor. It effectively reduces the peak current of Nav1.2 with an IC50 of 7.79 μM. Nav1.2-IN-1 demonstrates antiepileptic activity and shows strong anticonvulsant effects with low neurotoxicity in a subcutaneous pentylenetetrazol (sc-PTZ) induced seizure model.

NaV1.2/1.6 channel blocker-1 is a potent inhibitor of NaV1.2 and NaV1.6 channels, exhibiting inhibitory effects on rNaV1.6 and hNaV1.2. This compound can be utilized in the study of generalized epilepsy and movement disorders.

GNE-616 is a highly potent, metabolically stable, orally bioavailable, and subtype-selective Nav1.7 inhibitor [Ki: 0.79 nM, Kd: 0.38 nM for hNav1.7] for the treatment of chronic pain.

XPC-6444 is a isoform-selective, and CNS-penetrant inhibitor of NaV1.6 with IC50 of41 nM for hNaV1.6,with anticonvulsant activity.

Anticonvulsant agent 9 (compound 4f) is an activator of the α1β2γ2GABA_A receptor, with an EC50 value of 1.24 μM. It inhibits the inactivation of Nav1.2 channels and exhibits significant anticonvulsant activity.

Photoswitchable Kv channel blocker (IC50 values are 2 and 64 μM at 500 nm and 380 nm respectively). Switches conformation from cis to trans at 500 nm and trans to cis at 380 nm. Exhibits minimal activity at Nav1.2 and L-type Ca2+ channels. Stimulates action potential firing of hippocampal neurons in vitro at 500 nm and restores visual responsiveness in blind mice at 380 nm. Fortin et al (2008) Photochemical control of endogenous ion channels and cellular excitability. Nat.Methods 5 331 PMID:18311146 |Polosukhina et al (2012) Photochemical restoration of visual responses in blind mice. Neuron 75 271 PMID:22841312 |Banghart et al (2009) Photochromic blockers of voltage-gated potassium channels. Angew.Chem.Int.Ed. 48 9097 PMID:19882609

Lu AE98134, an activator of voltage-gated sodium channels, acts as a partly selective positive modulator of Nav1.1 channels and also increases the activity of Nav1.2 and Nav1.5 channels while not affecting Nav1.4, Nav1.6, and Nav1.7 channels. Lu AE98134 can be used to analyze pathophysiological functions of the Nav1.1 channel in various central nervous system diseases, including cognitive restoring in schizophrenia, et al[1].

4,9-Anhydrotetrodotoxin (4,9-anhydro-TTX) is a derivative of TTX that selectively blocks inward sodium current through Nav1.6 voltage-activated sodium channels (IC50 = 7.8 nM in Xenopus oocytes). [1][2][3] It demonstrates IC50 values of 1.3, 0.34, 0.99, 78.5, 1.3, and >30 µM for Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.7, and Nav1.8, respectively.[1]

GDC-0310 is a selective acyl-sulfonamide inhibitor targeting the Na_v1.7 channel, with a potent inhibitory concentration (IC_50) of 0.6 nM against hNa_v1.7.

PD-85639 is a voltage-gated sodium (Na+) channel blocker (75% in 10 min & >95% in 25 min blockage of Na+ current by 25 μM PD85,639; whole-cell patch clamp using primary rat brain neurons) that is shown to target rat brain Nav1.2 with simultaneous high- and low-affinity modes of binding (EC50 = 56 nM 40% & 20 μM 60% at pH 9.0, 5 nM 28% & 3 μM 72% at pH 7.4, against 2 nM [3H]-PD85,639 for binding rat brain synaptosomes; EC50 = 17 nM 39% & 10 μM 61% using at pH 9.0 using rat brain synaptosome membranes) and a fast kinetic (t1 2 = 1.2 at 4°C, <0.5 min at 25°C), competitive against the local anesthetic Na+ channel blockers tetracaine, bupivacaine, and mepivacaine, as well as Na+ channel activators veratridine and batrachotoxin (K1 = 0.26 μM against 5 nM [3H]-BTX for binding rat neocrotical membranes).

AA43279 is a novel selective Nav1.1 activator, increasing the firing activity of parvalbumin-expressing, fast-spiking GABAergic interneurons and increasing the spontaneous inhibitory post-synaptic currents (sIPSCs) recorded from pyramidal neurons.

ICA-121431 (2,2-Diphenyl-N-[4-(thiazol-2-ylsulfamoyl) is a nanomolar potent small molecule Nav1.7 channel inhibitor with IC50 of 19 nM for rat Nav1.7, with little or no activity against human Nav1.5 or Nav1.7 channels.

Phrixotoxin 3 TFA is a potent inhibitor of voltage-gated sodium channels, with IC50 values of 0.6 nM for NaV1.2, 42 nM for NaV1.3, 72 nM for NaV1.4, 288 nM for NaV1.1, and 610 nM for NaV1.5. This compound modulates the activity of these channels similarly to traditional gating-modifier toxins, inducing a depolarizing shift in gating kinetics and obstructing the inward sodium current.

Huwentoxin-IV TFA is a potent, selective blocker of sodium channels, specifically inhibiting neuronal Nav1.7, Nav1.2, Nav1.3, and Nav1.4 with IC50 values of 26, 150, 338, and 400 nM, respectively. It preferentially targets the peripheral nerve subtype Nav1.7 by interacting with neurotoxin receptor site 4, demonstrating analgesic effects in animal models of inflammatory and neuropathic pain [1] [2].

μ-Conotoxin KIIIA, an analgesic compound derived from Conus kinoshitai, selectively inhibits mammalian neuronal voltage-gated sodium channels (VGSCs) (Nav1.2), offering potential utility in pain research [1] [2].

GrTx1, a peptide toxin derived from Grammostola rosea spider venom, selectively inhibits sodium channels Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.6, and Nav1.7, with IC50 values of 0.63 µM, 0.23 µM, 0.77 µM, 1.29 µM, 0.63 µM, and 0.37 µM, respectively [2]. This compound has applications in neurological disease research [1].

GsAF-I is a potent blocker of Na_v and hERG1 channels, exhibiting half-maximal inhibitory concentrations (IC50s) of 0.36 μM (Na_v 1.1), 0.6 μM (Na_v 1.2), 1.28 μM (Na_v 1.3), 0.33 μM (Na_v 1.4), 1.2 μM (Na_v 1.6), 0.04 μM (Na_v 1.7), and 4.8 μM (hERG1) [1].

Phlo1b (μ-TrTx-Phlo1b), a 35-amino acid peptide toxin, selectively inhibits Nav1.7 channels with minimal inhibition of Nav1.2 and Nav1.5 [1].

Phlo1a (μ-TrTx-Phlo1a), a 35-amino acid peptide toxin, demonstrates a weak inhibitory effect on Nav1.2 and Nav1.5 channels [1]. Meanwhile, Phlo1b acts as a selective inhibitor of the Nav1.7 channel.

Ceratotoxin-2 (CcoTx2) is a voltage-gated sodium channel inhibitor with half maximal inhibitory concentrations (IC50) of 8 nM for Na v 1.2 β 1 and 88 nM for Na v 1.3 β 1 [1].

Ceratotoxin-1 (CcoTx1) is a peptide toxin that functions as an inhibitor of various voltage-gated sodium channel subtypes. It selectively inhibits Nav1.1 β1, Nav1.2 β1, Nav1.4 β1, and Nav1.5 β1 with IC50 values of 523 nM, 3 nM, 888 nM, and 323 nM, respectively. Additionally, Ceratotoxin-1 is known to inhibit Nav1.8 β1 [1].

Iota-conotoxin RXIA, an agonist of voltage-gated sodium channels (Na v 1.2, 1.6, 1.7), has been shown to induce repetitive action potentials and seizure in the motor axons of frogs following intracranial injection in mice [1].

XPC-5462 effectively inhibits NaV1.6 and NaV1.2 channels with IC50 values of 10.9 nM and 10.3 nM, respectively, and reduces epileptiform activity in an ex vivo brain slice seizure model [1].

Potent blocker of voltage-gated sodium channels (IC50 values are 0.6, 42, and 72 nM for NaV1.2, NaV1.3 and NaV1.5 respectively). Blocks inward sodium currents in a voltage-dependent manner.