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ShK-186

Dalazatide, ShK-186 [SL5]

A Potent Blocker of KV1.3

Cat #: STS-390
Alternative Name Dalazatide, ShK-186 [SL5]
Lyophilized Powder yes
  • Bioassay Tested
  • Origin Stichodactyla helianthus (Sun anemone) (Stoichactis helianthus)
    Source Synthetic peptide
    MW: 4441 Da
    Purity: >98% (HPLC)
    Form Lyophilized Powder
    Effective concentration 0.05 – 0.1 nM
    Sequence L-pTyr-AEEA -RSCIDTIPKSRCTAFQCKHSMKYRLSFCRKTCGTC-NH2
    Modifications Disulfide bonds location - Cys3-Cys35, Cys12-Cys28 and Cys17-Cys32.
    Cys35- C-terminal amide.
    L-phosphotyrosine attached to the Arg1 at N-terminus via an AEEA linker (2-aminoethoxy-2-ethoxy acetic acid; mini-PEG).
    Structure
    Molecular formula C184H296N57O55S7P1
    Activity ShK-186 is a potent and selective blocker of Kv1.3 voltage-gated K+ channels1.
    References-Activity
    1. Pennington, M. W. et al. (2009) Mol. Pharmacol., 75, 762.
    Shipping and storage Shipped at room temperature. Product as supplied can be stored intact at room temperature for several weeks. For longer periods, it should be stored at -20°C. Protect from light and moisture.
    Solubility Soluble in DDW.
    Centrifuge all products before use (10000 x, g 5 min). It is recommended to prepare fresh solutions in working buffers before use, or aliquot stock solutions reconstituted in distilled water and keep at -20°C. Upon use, dilute the stock solution in the desired working buffer. Prevent repeated thawing and freezing cycles.
    Storage of solutions Store up to one week at 4°C or up to 6 months at -20°C.
    Our bioassay
    • Alomone Labs ShK-186 blocks KV1.3 channels expressed in Xenopus oocytes.
      Alomone Labs ShK-186 blocks KV1.3 channels expressed in Xenopus oocytes.
      A. Representative time course of ShK-186 (#STS-390) inhibition of normalized KV1.3 current. Membrane potential was held at -100 mV, current was elicited by a 100 ms voltage ramp to +50 mV every 10 sec, and significantly inhibited by 0.1 nM (green) ShK-186.
      B. Superimposed traces of KV1.3 channel currents in the absence (control) and presence of 0.1 nM (green) ShK-186 (taken from the recording in A).
    References - Scientific background
    1. Castaneda, O. et al. (1995) Toxicon, 33, 603.
    2. Kalman,K. et al. (1998) J. Biol. Chem., 273, 32697.
    3. Beeton, C. et al. (2005) Mol. Pharmacol., 67, 1369.
    4. Pennington, M. W. et al. (2009) Mol. Pharmacol., 75, 762.
    5. Chandy, K.G. et al. (2017) Curr. Opin. Chem. Biol., 38, 97.
    6. Cahalan, M.D. et al. (2009) Immunol. Rev., 231, 59.
    7. Chang, S.C. et al.  (2018) WikiJournal of Science, 1, 1.
    8. Pennington, M.W. et al. (2018) Bioorg. Med. Chem., 26, 2738.
    9. Smallwood T.B. et al. (2021) Exp. Opin. Drug Disc. 1.
    Scientific background

    ShK-186 is a synthetic analog of ShK (#STS-400), a native 35 amino acid peptidyl toxin originally isolated from the nematocyst of the sea anemone Stichodactyla helianthus1. Native ShK blocks the voltage-gated potassium (KV)1.3, KV1.1, KV1.4, and KV1.6 at subnanomolar concentrations2. Its synthetic analog, ShK-186, is a highly specific Kv1.3 blocker with picomolar affinity and exhibited greater than 100-fold selectivity for Kv1.3 over Kv1.1 and other channels3,4. ShK-186 contains negatively charged amino acid L-phosphotyrosine attached to the N terminus via an AEEA (mini-PEG) hydrophilic linker and is amidated at C-terminus4.

    Kv channels play key roles in human physiology and pathology. The Kv1.3 channel in T lymphocytes is a validated therapeutic target for diverse autoimmune diseases5. This channel maintains the membrane potential of a sub-set of T lymphocytes known as effector memory (TEM) T cells, that mediate and play a major role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes mellitus, rheumatoid arthritis (RA), and psoriasis4,6. ShK-186 (a.k.a. dalazatide) has been shown to be effective against autoimmune diseases in several models and being advanced as a treatment for multiple diseases, including inclusion body myositis, lupus, ANCA vasculitis, MS, psoriasis, psoriatic arthritis, RA, type 1 diabetes, inflammatory bowel diseases, and asthma. Moreover, proof of concept has been demonstrated for dalazatide therapy in a phase 1b psoriasis study 7-9.

    Target Kv1.3
    Peptide Content: 100%
    Last update: 29/08/2021

    ShK-186 (#STS-390) is a highly pure, synthetic, and biologically active peptide toxin.

    For research purposes only, not for human use
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