Overview
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).
- Pennington, M. W. et al. (2009) Mol. Pharmacol., 75, 762.
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.
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).
- Castaneda, O. et al. (1995) Toxicon, 33, 603.
- Kalman,K. et al. (1998) J. Biol. Chem., 273, 32697.
- Beeton, C. et al. (2005) Mol. Pharmacol., 67, 1369.
- Pennington, M. W. et al. (2009) Mol. Pharmacol., 75, 762.
- Chandy, K.G. et al. (2017) Curr. Opin. Chem. Biol., 38, 97.
- Cahalan, M.D. et al. (2009) Immunol. Rev., 231, 59.
- Chang, S.C. et al. (2018) WikiJournal of Science, 1, 1.
- Pennington, M.W. et al. (2018) Bioorg. Med. Chem., 26, 2738.
- Smallwood T.B. et al. (2021) Exp. Opin. Drug Disc. 1.
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.
ShK-186 (#STS-390) is a highly pure, synthetic, and biologically active peptide toxin.
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