Ion Channel Modulators

Phrixotoxin 2 is a Kv4 family potassium channel inhibitor, with K_i values in rats of 120 nM for Kv4.2, 110 nM for Kv4.3, and 230 nM for Kv4.1. Phrixotoxin 2 mediates voltage-dependent inhibition of Kv4.2 and Kv4.3 currents, and voltage-independent inhibition of Kv4.1 currents. Phrixotoxin 2 fails to inhibit A-type K⁺ currents in visceral dorsal root ganglion neurons. Phrixotoxin 2 induces contraction of non-pregnant uterine smooth muscle and triggers orofacial cold hyperalgesia in rats. Phrixotoxin 2 can distinguish the contribution of Kv4 subunits to A-type K⁺ currents in different subsets of sensory neurons. Phrixotoxin 2 can be used in research related to chronic pain and trigeminal neuropathic pain.

GsAF-II is a peptide toxin that blocks hERG1 subtype potassium channels in a voltage-dependent manner. GsAF-II blocks Nav1.x subtype sodium channels.

Huwentoxin I (HWTX-I) is a peptide toxin that inhibits voltage-gated sodium channels and N-type calcium channels. Huwentoxin I inhibits sodium channels in rat hippocampus and cockroach dorsal unpaired median (DUM) neurons with IC₅₀ values of 66.1 and 4.80 nM, respectively.

VSTx-3 is a K_V channel blocker. VSTx-3 is demonstrated to be a potent, TTX-sensitive sodium channel blocker and especially, a potent blocker of NaV1.8 channels (IC₅₀ 0.19 μM for hNaV1.3, 0.43 μM for hNaV1.7 and 0.77 μM for hNaV1.8 channels).

Cd1a is a β-toxin derived from the African spider Ceratogyrus darlingi. Cd1a can regulate calcium ion channels. Cd1a inhibits human calcium ion channels (Ca_v2.2)(IC₅₀2.6 μM) and mouse sodium ion channels (Na_v1.7). Cd1a can be used in the development of peripheral pain treatment drugs .

Cn2 toxin is aβ- toxoins. Cn2 toxin can bind to the voltage sensing domain of voltage gated sodium channels (Na_v) .

Ergtoxin-1 is a potassium channel blocker. Ergtoxin-1 is isolated from the venom of the Mexican scorpion Centruroides noxius. Ergtoxin 1 can block ERG-K⁺ channels in nerve, heart and endocrine cells.

PLTX-II is a calcium channel blocker. PLTX-II has a 44-residue peptide containing ten Cys residues and an O-palmitoylated threonine amide at the carboxy-terminus.

Tityustoxin-Kα (TsTx-Kα) is an inhibitor of potassium voltage-gated channels. Tityustoxin-Kα shows a dose-dependent block of the sustained outward current in cultured hippocampal neurons .

Urotoxin is an inhibitor of the potassium channel. Urotoxin has a selective affinity for hKv1.2 channel.

Vm24-toxin (Vaejovis mexicanus peptide 24), a 36-residue peptide, is a potent and selective Kv1.3 blocker with a K_d of ~3 pM in lymphocytes. Vm24-toxin shows >1500-fold affinity for Kv1.3 over other assayed potassium channels. Vm24-toxin folds into a distorted cystine-stabilized α/β motif consisting of a single-turn α-helix and a three-stranded antiparallel β-sheet, stabilized by four disulfide bridges. Vm24-toxin attenuates the CD4⁺ effector memory T cell response to T cell receptor (TCR) stimulation.

Anthopleurin-C (APE 2-1) is a cardiotonic polypeptide that shows a powerful positive inotropic effect.

BDS-II is a peptide toxin, and is composed of 43 amino acids. BDS-II is a selective Kv3.4 channel inhibitor.

Heteropodatoxin-2, a peptides of 30-amino acid, is a heteropodatoxin. Heteropodatoxin-2 blocks Kv4.2 current expressed in Xenopus laevis oocytes in a voltage-dependent manner, with less block at more positive potentials.

δ-Buthitoxin-Hj1a, a scorpion-venom peptide, is a potent NaV1.1 agonist with an EC₅₀ of 17nM. δ-Buthitoxin-Hj1a can be used for the Dravet syndrome (DS) research.

δ-Buthitoxin-Hj2a, a scorpion-venom peptide, is a potent NaV1.1 agonist with an EC₅₀ of 32 nM. δ-Buthitoxin-Hj2a can be used for the Dravet syndrome (DS) research.

δ-Theraphotoxin-Hm1b is a 42-amino acid peptide isolated from Togo starburst tarantula (Heteroscodra maculata) venom. δ-Theraphotoxin-Hm1b selectively inhibits inactivation of NaV1.1 but have no effect on NaV1.7.

π-TRTX-Hm3a is a 37-amino acid peptide isolated from Togo starburst tarantula (Heteroscodra maculata) venom. π-TRTX-Hm3a pH-dependently inhibits acid-sensing ion channel 1a (ASIC1a) with an IC₅₀ of 1-2 nM and potentiates ASIC1b with an EC₅₀ of 46.5 nM.

Jingzhaotoxin-II, a 32 amino acid residues including two acidic and two basic residues, is a neurotoxin. Jingzhaotoxin-II inhibits voltage-gated sodium channels (VGSC) that significantly slows rapid inactivation of TTX-resistant (TTX-R) VGSC on cardiac myocytes with the IC₅₀ of 0.26 μM.

Jingzhaotoxin-IX, a C-terminally amidated peptide composed of 35 amino acid residues, is a neurotoxin. Jingzhaotoxin-IX inhibits voltage-gated sodium channels (both tetrodotoxin-resistant and tetrodotoxin-sensitive isoforms) and Kv2.1 channel. Jingzhaotoxin-IX has no effect on delayed rectifier potassium channel Kv1.1, 1.2 and 1.3.