VSTx-3 is a potassium voltage-gated channel (K_V) blocker, which has also been shown to be a potent tetrodotoxin-sensitive (TTX-sensitive) sodium channel inhibitor, with particular efficacy against NaV1.8 channels, as evidenced by its half-maximal inhibitory concentration (IC_50) values of 0.19 μM for hNaV1.3, 0.43 μM for hNaV1.7, and 0.77 μM for hNaV1.8 channels.

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].

Cn2 toxin, a β-toxin, interacts with the voltage-sensing domain of voltage-gated sodium channels (NaV) [1].

Potent and selective, voltage-dependent R-type CaV2.3 calcium channel blocker (IC50 = 30 nM). Antinociceptive; inhibits nociceptive C-fibre and Aδ-fibre-evoked neuronal responses.

Tityustoxin-Kα (TsTx-Kα) acts as an inhibitor of potassium voltage-gated channels, exhibiting a dose-dependent blockade of the sustained outward current in cultured hippocampal neurons [1].

Kurtoxin is a selective Cav3 (T-type) voltage-gated Ca2+ channel gating inhibitor, exhibiting a dissociation constant (Kd) of 15 nM for the Cav3.1 (α1G T-type) Ca2+ channel. The compound demonstrates high-affinity interactions with native neuronal high-threshold L-type, N-type, and P-type Ca2+ channels in both central and peripheral neurons, while also displaying cross-reactivity with the voltage-gated Na+ channel [1].

Iberiotoxin (TFA) is a selective inhibitor of high conductance Ca2+-activated K+ channels, exhibiting a dissociation constant (Kd) of approximately 1 nM, yet it does not inhibit other types of voltage-dependent ion channels [1] [2] [3].

Guangxitoxin 1E acts as a gating modifier since it shifts the voltage-dependence of Kv2.1 K+ currents towards depolarized potentials.

μ-Conotoxin BuIIIB (Mu-Conotoxin BuIIIB), a selective blocker of mammalian neuronal voltage-gated sodium channels (VGSC), is derived from Cone snail venom and serves as a research probe for ion channel function, as well as in the investigation of neurological disorders like pain [1].

Heteropodatoxin-2, a 30-amino acid peptide, inhibits the Kv4.2 current in Xenopus laevis oocytes through a voltage-dependent mechanism, exhibiting reduced blocking at more positive potentials [1].

Tat-CBD3A6K, a peptide derivative of the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2) interaction inhibitor Tat-CBD3, has demonstrated efficacy in a rat model of antiretroviral neuropathic pain caused by stavudine (d4T). Administered at 10 mg/kg, it preserves paw withdrawal threshold, indicating pain relief, and reduces the number of action potentials in dorsal root ganglia (DRG) neurons from affected rats. Additionally, a 30 µM/animal dural dose of Tat-CBD3A6K lessens meningeal blood flow escalation triggered by capsaicin, showcasing its potential in managing neuropathic pain and inflammation.

Myr-Tat-CBD3 is a chemical compound that serves as an inhibitor of the protein-protein interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2). This compound effectively disrupts the Cav2.2-CRMP2 interaction by about 81% at a 10 µM concentration and demonstrates an inhibitory concentration 50 (IC50) value of approximately 2.8 µM against potassium-induced calcium influx in primary rat dorsal root ganglion (DRG) neurons. Furthermore, at a concentration of 20 µM, Myr-Tat-CBD3 specifically inhibits calcium currents without affecting sodium currents in primary DRG neurons. Additionally, intrathecal administration of 20 µg/5 µl of Myr-Tat-CBD3 effectively mitigates carrageenan-induced declines in paw withdrawal latencies in rats, indicating its potential for pain relief. The compound also notably reduces cue-induced reinstatement of cocaine-seeking behavior in rats, suggesting therapeutic potential in addiction treatment.

Selective NaV1.7 channel blocker. Preferentially inhibits neuronal NaV1.7, 1.2 and 1.3 (IC50 values are 26, 150 and 338 nM respectively), compared to muscle subtypes NaV1.4 and 1.5 (IC50 = >10 μM). Inhibits the channel by binding at the neurotoxin recepto

GTx1-15, an inhibitor cystine knot (ICK) peptide, antagonizes the voltage-dependent calcium channel Cav3.1, as well as voltage-dependent sodium channels Nav1.3 and Nav1.7 [1].

ω-Conotoxin CVIA, a 27-amino acid neuropeptide, functions as a blocker of voltage-sensitive calcium channels (VSCCs) [1].

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].

Noxiustoxin, a toxin extracted from the venom of the Mexican scorpion Centruroides noxius, inhibits both the voltage-dependent potassium channel (Kv1.3, IC50 = 360 nM) and the calcium-activated potassium channel. It is significant in the pathophysiology of neuroinflammatory diseases [1] [2].

GsAF-II is a peptide toxin that selectively blocks hERG1 subtype potassium channels through a voltage-dependent mechanism and impedes Nav1.x subtype sodium channels [1].

Calcicludine, a protein toxin derived from the green mamba (Dendroaspis angusticeps) venom, selectively inhibits high-voltage-activated, particularly L-type, calcium channels with an IC50 of 88 nM and plays a role in excitatory synaptic transmission [1] [2].

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.

β-Bag cell peptide, a neuroactive peptide, elevates cyclic AMP levels and reduces the amplitudes of voltage-dependent potassium currents [1] in bag cell neurons.

Atosiban (RW22164) is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant (tocolytic) to halt premature labor. Atosiban inhibits the oxytocin-mediated release of inositol trisphosphate from the myometrial cell membrane. As a result, there is reduced release of intracellular, stored calcium from the sarcoplasmic reticulum of myometrial cells, and reduced influx of Ca2+ from the extracellular space through voltage gated channels. In addition, atosiban suppresses oxytocin-mediated release of PGE and PGF from the decidua. In human pre-term labor, atosiban, at the recommended dosage, antagonizes uterine contractions and induces uterine quiescence. The onset of uterus relaxation following atosiban is rapid, uterine contractions being significantly reduced within 10 minutes to achieve stable uterine quiescence.

mHuwentoxin-IV, a naturally modified form of Huwentoxin-IV, selectively inhibits tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels in dorsal root ganglion neurons with an IC50 value of 54.16 nM. Notably, the inhibitory effect of mHuwentoxin-IV on these sodium channels is unaffected by strong depolarization voltages [1].

Jingzhaotoxin-IX is a C-terminally amidated peptide neurotoxin consisting of 35 amino acid residues. It inhibits both tetrodotoxin-resistant and tetrodotoxin-sensitive isoforms of voltage-gated sodium channels, as well as the Kv2.1 channel. However, Jingzhaotoxin-IX does not affect the delayed rectifier potassium channels Kv1.1, Kv1.2, and Kv1.3 [1].

μ-Conotoxin BuIIIA (Mu-Conotoxin BuIIIA), a toxin derived from Cone snail venom, functions as a voltage-gated sodium channel (VGSC) blocker. This toxic peptide is utilized in researching neurological diseases [1].

κM-Conotoxin RIIIK is a potassium channel antagonist that inhibits voltage-activated potassium ion channels [1].

Egg-laying hormone (ELH) is a neuropeptide synthesized by the bag cell neurons, Egg-laying hormone (ELH) induces egg laying and its correlated behavior in Aplysia californica. Egg-laying hormone (ELH) has been purified to homogeneity and Egg-laying hormon

β-Defensin-1 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.1It inhibits the growth ofB. adolescentis,L. acidophilus,B. breve,B. vulgatus,L. fermentum,B. longum, andS. thermophilusin an antimicrobial radial diffusion assay.2β-Defensin-1 also inhibits the growth of periodontopathogenic and cariogenic bacteria, includingP. gingivalisandS. salivarius, and of susceptibleM. tuberculosisH37Rv but not of resistantM. tuberculosisRM22 when used at a concentration of 128 μg/ml.3,4It blocks human and mouse Kv1.3 voltage-gated potassium channels (IC50s = 11.8 and 13.2 μM, respectively).5Overexpression of β-defensin-1 in the human oral squamous cell carcinoma (OSCC) cell lines HSC-3, UM-1, and SCC-9 increases migration and invasion but not proliferation.6 1.Lehrer, R.I.Primate defensinsNat. Rev. Microbiol.2(9)727-738(2004) 2.Schroeder, B.O., Ehmann, D., Precht, J.C., et al.Paneth cell α-defensin 6 (HD-6) is an antimicrobial peptideMucosal Immunol.8(3)661-671(2015) 3.Ouhara, K., Komatsuzawa, H., Yamada, S., et al.Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cellsJ. Antimicrob. Chemother.55(6)888-896(2005) 4.Fattorini, L., Gennaro, R., Zanetti, M., et al.In vitro activity of protegrin-1 and beta-defensin-1, alone and in combination with isoniazid, against Mycobacterium tuberculosisPeptides25(7)1075-1077(2004) 5.Feng, J., Xie, Z., Yang, W., et al.Human beta-defensin 1, a new animal toxin-like blocker of potassium channelToxicon113(2016) 6.Han, Q., Wang, R., Sun, C., et al.Human beta-defensin-1 suppresses tumor migration and invasion and is an independent predictor for survival of oral squamous cell carcinoma patientsPLoS One9(3)e91867(2014)

Scorpion toxin Tf2, a β-scorpion toxin first identified in the venom of the Brazilian scorpion Tityus fasciolatus, acts as an activator of the neuronal voltage-gated sodium (Nav) subtype Nav1.3, associated with epilepsy and nociception. It increases hNav1.3 activation voltage, prompting channel opening at resting membrane potentials [1].

ω-Hexatoxin-Hv1a, a neurotoxin extracted from the venom of the spider Hadronyche versuta, inhibits voltage-gated calcium channels [1] [2].

AF2 is the nematode neuropeptide. It also increases voltage-activated calcium currents in Ascaris suum muscle.

Ceratotoxin-2 (CcoTx2) is a voltage-gated sodium channel inhibitor, demonstrating 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].

Tat-CBD3 is a chemical compound inhibiting the interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2), as well as the interaction between CRMP2 and the NMDA receptor NR2B subunit. At a concentration of 10 µM, Tat-CBD3 reduces the Cav2.2-CRMP2 interaction by 43% in cell-free assays and impedes the NMDA receptor NR2B subunit-CRMP2 interaction in immunoprecipitation assays. It lowers voltage-induced calcium currents by about 60% in primary rat dorsal root ganglion (DRG) neurons and decreases glutamate-induced cytosolic calcium level rises in primary rat hippocampal neurons. When administered at 20 mg/kg, Tat-CBD3 lessens infarct volume in a rat model of cerebral ischemia following middle cerebral artery occlusion (MCAO). Additionally, intrathecal delivery of Tat-CBD3 at a dose of 20 µg/5 µl mitigates carrageenan-induced thermal hypersensitivity in rats.

Phrixotoxin 2 selectively blocks the KV 4.2 and KV 4.3 channels, demonstrating high specificity in its interaction with these voltage-gated ion channels [1].

Huwentoxin I (HWTX-I) is a peptide toxin that targets and inhibits both voltage-gated sodium channels and N-type calcium channels. It effectively inhibits sodium channels in the rat hippocampus and cockroach dorsal unpaired median (DUM) neurons, displaying IC50 values of 66.1 nM and 4.80 nM, respectively [1].

ProTx-III, a spider venom peptide derived from the Peruvian green velvet tarantula, functions as a selective and potent inhibitor of the voltage-gated sodium channel Na v 1.7, exhibiting an IC 50 of 2.1 nM. Characterized by its inhibitor cystine knot motif (ICK), ProTx-III can attenuate the pain response and is applicable in research on chronic pain, epilepsy, and arrhythmia [1].

Phrixotoxin 3 TFA is a potent inhibitor of voltage-gated sodium channels, demonstrating 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, respectively. This compound modulates the activity of these channels similarly to traditional gating-modifier toxins, inducing a depolarizing shift in gating kinetics as well as obstructing the inward sodium current.

SOR-C13 TFA, a truncated carboxy-terminal peptide, serves as a potent TRPV6 antagonist, demonstrating high affinity with an IC 50 value of 14 nM. TRPV6, a non-voltage-gated calcium channel linked to malignancy and poor prognosis in breast cancer, is effectively targeted by SOR-C13 TFA, indicating its anticancer activity [1].

Huwentoxin XVI TFA, a potent analgesic derived from the Chinese tarantula Ornithoctonus huwena, acts as a highly reversible and selective antagonist of mammalian N-type calcium channels (IC 50 of ~60 nM), with no impact on voltage-gated T-type calcium channels, potassium channels, or sodium channels [1].

Atosiban acetate (RW22164) is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant (tocolytic) to halt premature labor. Atosiban acetate (RW22164) inhibits the oxytocin-mediated release of inositol trisphosphate from the myometrial cell membrane. As a result, there is reduced release of intracellular, stored calcium from the sarcoplasmic reticulum of myometrial cells, and reduced influx of Ca2+ from the extracellular space through voltage gated channels. In addition, Atosiban acetate (RW22164) suppresses oxytocin-mediated release of PGE and PGF from the decidua. In human pre-term labor, atosiban, at the recommended dosage, antagonizes uterine contractions and induces uterine quiescence. The onset of uterus relaxation following atosiban is rapid, uterine contractions being significantly reduced within 10 minutes to achieve stable uterine quiescence.

Jingzhaotoxin-II, a neurotoxin composed of 32 amino acid residues featuring two acidic and two basic residues, selectively inhibits voltage-gated sodium channels (VGSC), notably slowing the rapid inactivation of TTX-resistant (TTX-R) VGSC in cardiac myocytes, with an IC50 of 0.26 μM [1].

ω-Conotoxin CVIE selectively inhibits voltage-gated Ca^2+ channels (Ca_v 2.2) [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].

Ssm Spooky Toxin, derived from Scolopendra mutilans, exhibits potent lethality affecting both hematological and respiratory systems primarily through the inhibition of KCNQ (voltage-gated potassium channel family 7) channels. It demonstrates IC50 values of 2.8 μM for Kv7.4, 5.26 μM for Kv1.3, and 0.1-0.3 M for the Shal channel, respectively. Additionally, this toxin impedes cytokine production by selectively targeting the KV1.3 channel in T cells and is crucial for the centipede's circulatory system functions [1] [2] [3].

ω-Conotoxin CVIB is an antagonist of non-selective N- and P/Q-type voltage-gated calcium channels (VGCCs). It inhibits depolarization-activated whole-cell VGCC currents in dorsal root ganglion (DRG) neurons, exhibiting a pIC50 of 7.64 [1].

KTX-Sp2, a potassium channel toxin, effectively blocks exogenous voltage-gated potassium channels Kv1.1, Kv1.2, and Kv1.3, as well inhibits the endogenous Kv1.3 channel and suppresses Ca2+ signaling in Jurkat T cells. Additionally, KTX-Sp2 inhibits IL-2 secretion from activated Jurkat T cells [1].

ω-Conotoxin SO3 is an analgesic peptide that functions as an antagonist to N-type voltage-sensitive calcium channels, and can be isolated from the venom of Conus striatus [1] [2].

Hainantoxin-IV acts as a specific antagonist for tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels, with His28 and Lys32 being critical residues for binding to the target. This compound also features an inhibitor cystine knot motif [1].

Dendrotoxin-I, a neurotoxin from Dendroaspis snake venom, potently blocks K⁺ channels, specifically targeting voltage-gated potassium channel subunits KV1.1 and KV1.2 [1] [2] [3].

ShK toxin, isolated from the Caribbean sea anemone (Stichodactyla helianthus), is an inhibitor of the voltage-dependent potassium channel (Kv1.3 channel). It competes with dendrotoxin I and α-dendrotoxin in binding to rat brain synaptosomal membranes and promotes acetylcholine release. Additionally, ShK toxin reduces K+ currents in cultured rat dorsal root ganglion neurons and inhibits T lymphocyte proliferation [1] [2].