Ion Channel Modulators

Crotamine TFA is a Na⁺ channel modulator. Crotamine is a 42 amino acid toxin cross-linked by three disulfide bridges. Crotamine has analgesic activity. Crotamine also interacts with lipid membranes and shows myonecrotic activity. Crotamine can be isolated from Crotalus durissus terrificus venom.

HsTX1 (TFA) toxin, from the scorpion Heterometrus spinnifer, is a 34-residue, C-terminally amidated peptide cross-linked by four disulfide bridges. HsTX1 (TFA) is an the inhibitor of potassium channel, with IC₅₀ for Kv1.3 of 12 pM and inhibits T_EM cell activation and attenuates inflammation in autoimmunity.

Apamin TFA (Apamine TFA) is an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is known as a specifically selective blocker of Ca²⁺-activated K⁺ (SK) channels and exhibits anti-inflammatory and anti-fibrotic activity.

Cn2 toxin TFA (β-Mammal toxin Cn2 TFA) is a single-chain β-scorpion neurotoxic peptide that is the main toxin in scorpion venom. Cn2 toxin (TFA) specifically targets mammalian voltage-gated sodium channels (VGSC) Nav1.6.

ω-Agatoxin TK, a peptidyl toxin of the venom of Agelenopsis aperta, is a potent and selective P/Q type Ca²⁺ channel blocker. ω-Agatoxin TK inhibits the high K⁺ depolarisation-induced rise in internal Ca²⁺ in cerebral isolated nerve endings with an IC₅₀ of of 60 nM. ω-Agatoxin TK has no effect on L-type, N-type, or T-type calcium channels.

GaTx2 is a seletive and a high affinity inhibitor of ClC-2 channels with a voltage-dependent apparent K_D of ∼20 pM. GaTx2 is a peptide toxin inhibitor from Leiurus quinquestriatus hebraeus venom. GaTx2 is useful in determining the role and the membrane localization of ClC-2 in specific cell types.

APETx2 TFA, a sea anemone peptide from Anthopleura elegantissima, is a selective and reversible ASIC3 inhibitor, with an IC₅₀ of 63 nM. APETx2 directly inhibits the ASIC3 channel by acting at its external side. APETx2 could reverses acid‐induced and inflammatory pain.

Jingzhaotoxin-XII (JzTx-XII) TFA is a specific Kv4.1 channel inhibitor with an IC₅₀ of 0.363 μM. Jingzhaotoxin-XII TFA interacts with the channels by modifying the gating behavior.

Charybdotoxin, a 37-amino acid peptide, is a K⁺ channel blocker.

ShK toxin TFA (Stichodactyla helianthus neurotoxin TFA) is a neurotoxin. ShK toxin TFA blocks voltage-dependent potassium channel (K_v1.3 channel). ShK toxin TFA can be isolated from the whole body extract of the Caribbean sea anemone (Stichodactylu helianthus). ShK toxin TFA competes with dendrotoxin I and α-dendrotoxin for binding to synaptosomal membranes of rat brain, facilitates acetylcholine release. ShK toxin TFA suppresses K⁺ currents in cultured rat dorsal root ganglion neurons. ShK toxin TFA also inhibits T lymphocyte proliferation.

Vm24-toxin (Vaejovis mexicanus peptide 24) TFA, a 36-residue peptide, is a potent and selective Kv1.3 blocker with a K_d of ~3 pM in lymphocytes. Vm24-toxin TFA shows >1500-fold affinity for Kv1.3 over other assayed potassium channels. Vm24-toxin TFA 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 TFA attenuates the CD4⁺ effector memory T cell response to T cell receptor (TCR) stimulation.

GpTx-1 TFA is a peptide-based Na_V1.7 sodium channel antagonist isolated from the venom of the Chilean spider Grammostola porter. GpTx-1 TFA demonstrates potent inhibitory activity against the Na_V1.7 channel with an IC₅₀ value of 10 nM, while exhibiting excellent selectivity for Na_V1.4 (IC₅₀ = 0.301 μM) and Na_V1.5 (IC₅₀ = 4.20 μM), showing >20-fold and >950-fold selectivity respectively.

ADWX 1 TFA is a new peptide inhibitor that is potent and selective for Kv1.3 with an IC₅₀ value of 1.89 pM. ADWX 1 inhibits Kv1.3 channel activity specifically to inhibit both the initial calcium signaling and NF-κB activation. ADWX 1 TFA ameliorates the disease in rats of experimental autoimmune encephalomyelitis (EAE) models. ADWX 1 TFA can be used to study T cell-mediated autoimmune diseases.

Psalmotoxin 1 (PcTx1) TFA is a protein toxin that can bind at subunit-subunit interfaces of acid-sensing ion channel 1a (ASIC1a). Psalmotoxin 1 TFA is a potent and slective ASIC1a inhibitor (IC₅₀: 0.9 nM) by increasing the apparent affinity for H⁺ of ASIC1a. Psalmotoxin 1 TFA can induce cell apoptosis, also inhibits cell migration, proferliration and invasion of cancer cells. Psalmotoxin 1 TFA can be used in the research of cancers, or neurological disease.

(Trp63,Trp64)​-​C3a(63-77) is a C3a synthetic analogue peptide, which exhibits Ca²⁺ stimulating efficacy in human neutrophils and hC3aR or mC3aR expressing RBL-2H3 cells with EC₅₀ of 9.5, 2.0 and 0.8 nM, respectively.

Phrixotoxin-1 (TFA), from the venom of the theraphosid spider Phrixotrichus auratus, is a specific peptide inhibitor of Kv4 potassium channel.

OD1 is a scorpion α-toxin that can be isolated from the venom of the Iranian yellow scorpion (Odonthobuthus doriae. OD1 is a modulator of mammalian Nav1.7 (EC₅₀: 4.5 nM).

Mambalgin 1 TFA is a selective ASIC1a inhibitor (IC₅₀ values are 192 and 72 nM for human ASIC1a and ASIC1a/1b dimer, respectively). Mambalgin 1 TFA binds to closed/inactive channel. Mambalgin 1 TFA is selective for ASIC1a over ASIC2a, ASIC3, TRPV1, P2X2, 5-HT3, Nav1.8, Cav3.2 and Kv1.2 channels. Mambalgin 1 TFA increases latency of withdrawal response in mouse tail-flick and paw-flick tests.

β-Pompilidotoxin (β-PMTX), a wasp venom, can slow sodium channel inactivation and increases steady-state sodium current in cells.

CALP1 is a calmodulin (CaM) agonist (K_d of 88 µM) with binding to the CaM EF-hand/Ca²⁺-binding site. CALP1 blocks calcium influx and apoptosis (IC₅₀ of 44.78 µM) through inhibition of calcium channel opening. CALP1 blocks glutamate receptor channels and blocks a store-operated nonselective cation channel. CALP1 activates CaM-dependent phosphodiesterase activity.