kv1.3 channels

UK 78282 hydrochloride, a novel potent and selective Kv1.3 blocker.UK 78282 hydrochloride inhibits Kv1.3 voltage-gated potassium channels and suppresses human T cell activation.

PAP-1 (5-(4-Phenoxybutoxy)psoralen) is a selective, orally active Kv1.3 blocker with an EC50 of 2 nM.

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)

OSK-1 is a potent potassium channel blocker belonging to the α-KTx3 toxins. It exhibits IC50 values of 0.6 nM, 5.4 nM, and 0.014 nM for Kv1.1, Kv1.2, and Kv1.3 channels, respectively. Additionally, OSK-1 acts as a moderate blocker of the calcium-activated KCa3.1 channel, with an IC50 of 225 nM. Consequently, OSK-1 finds application as an immunosuppressive drug.

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].

Hemitoxin, a scorpion-venom peptide, acts as a K+ channel blocker, selectively inhibiting rat Kv1.1, Kv1.2, and Kv1.3 channels expressed in Xenopus oocytes, with IC50 values of 13 nM, 16 nM, and 2 nM, respectively [1].

Aam-KTX, a toxic peptide sourced from Mesobuthus eupeus scorpion venom, acts as a selective K_v channel inhibitor, exhibiting IC_50 values of 1.1 nM for K_v1.3 channels and >750 nM for K_v1.1 channels. This compound shows promise for research in autoimmune diseases [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].

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].

Ssm Spooky Toxin TFA, found in Scolopendra mutilans, effectively inhibits the KCNQ (voltage-gated potassium channel family 7) channels. Its IC50 values for Kv7.4, Kv1.3, and Shal channels are 2.8 μM, 5.26 μM, and 0.1-0.3 M, respectively. This toxin suppresses cytokine production by specifically targeting KV1.3 channels in T cells and plays a crucial role in the centipede's circulatory system.

Potent KV1.3 channel blocker (IC50 = 36 pM). Displays no effect at calcium-activated channels. Reduces VEGF-induced transmembrane calcium influxes and nitric oxide production in human endothelial cells.

Potent Shaker K+ channel blocker (Ki = 0.64 nM). Also inhibits Kv1.3, Kv1.6 and Kv1.1 K+ channels (Ki values are 4, 37 and 44 pM respectively).

Extremely potent KV1.3 channel blocker (Kd = 23 pM for mKV1.3 currents). Selective for KV1.3 over other mammalian potassium channels (IC50 values are 23, 1800, 10500, 37000 and 39000 pM for mKV1.3, mKV1.1, hKV1.6, mKV1.4 and rKV1.2 respectively, and >1000

ShK-Dap22 TFA is a potent and specific Kv1.3 immunosuppressive polypeptide. It acts as a selective Kv1.3 channel blocker, exhibiting IC50 values of 23 pM for mKv1.3, 1.8 nM for mKv1.1, 10.5 nM for hKv1.6, 37 nM for mKv1.4, and 39 nM for rKv1.2 channels.

Vm24-toxin (Vaejovis mexicanus peptide 24) TFA is a peptide composed of 36 amino acids, known for effectively and selectively blocking Kv1.3 channels, exhibiting an affinity (Kd) of approximately 3 pM in lymphocytes. It demonstrates over 1500 times greater affinity for Kv1.3 compared to other tested potassium channels. The structure of Vm24-toxin TFA includes a twisted cystine-stabilized α/β motif, comprising a single-turn α-helix and a three-stranded antiparallel β-sheet, stabilized by four disulfide bridges. Additionally, Vm24-toxin TFA can attenuate the response of CD4+ effector memory T cells to T-cell receptor (TCR) stimulation.

ShK toxin TFA (Stichodactyla helianthus neurotoxin TFA) is a neurotoxin that inhibits voltage-gated potassium channels (Kv1.3 channels). This toxin can be isolated from the crude extracts of the Caribbean sea anemone (Stichodactyla helianthus). It competes with Dendrotoxin I and α-dendrotoxin for binding to rat brain synaptosomal membranes, facilitating the release of acetylcholine. ShK toxin TFA suppresses K+ currents in cultured rat dorsal root ganglion neurons and also inhibits T lymphocyte proliferation.