ArticleThe Journal of pharmacology and experimental therapeutics2012
Durable pharmacological responses from the peptide ShK-186, a specific Kv1.3 channel inhibitor that suppresses T cell mediators of autoimmune disease.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed.
- Trial
- Recent advances in the pharmacology of voltage-gated ion channels.Pharmacological reviews · 2025Review
- Design and synthesis of novel small molecules targeting the Kv1.3 voltage-gated potassium ion channel.Scientific reports · 2025Article
- Limosilactobacillus reuteri enables oral-to-systemic absorption of iberiotoxin for treatment of collagen-induced arthritis in rats.Microbial cell factories · 2025Article
- Cnidarian toxins: omics approaches and recombinant proteins.The journal of venomous animals and toxins including tropical diseases · 2025Article
- Voltage-Gated KMarine drugs · 2024Review
- Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with granulomatosis with polyangiitis.Rheumatology (Oxford, England) · 2024Article
- Cyclic Peptides in Pipeline: What Future for These Great Molecules?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- A bioengineered probiotic for the oral delivery of a peptide Kv1.3 channel blocker to treat rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Adeno-Associated virus 8 delivers an immunomodulatory peptide to mouse liver more efficiently than to rat liver.PloS one · 2023Article
- Never, Ever Make an Enemy… Out of an Anemone: Transcriptomic Comparison of Clownfish Hosting Sea Anemone Venoms.Marine drugs · 2022Review
- Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators.Nature communications · 2022Article
- A Sea AnemoneToxins · 2022Article
- Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanisms Underlying C-type Inactivation in Kv Channels: Lessons From Structures of Human Kv1.3 and Fly Shaker-IR Channels.Frontiers in pharmacology · 2022Review
- Kv1.3 inhibition attenuates neuroinflammation through disruption of microglial calcium signaling.Channels (Austin, Tex.) · 2021Review
- Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction: regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications.Neural regeneration research · 2021Review
- The potassium channel Kv1.3 as a therapeutic target for immunocytoprotection after reperfusion.Annals of clinical and translational neurology · 2021Article
- Targeting inflammatory cytokine storm to fight against COVID-19 associated severe complications.Life sciences · 2021Review
12 more citing papers are in PubMed but not listed here.
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22 authors.
Funding
Abstract
The Kv1.3 channel is a recognized target for pharmaceutical development to treat autoimmune diseases and organ rejection. ShK-186, a specific peptide inhibitor of Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid arthritis. Here, we describe the pharmacokinetic-pharmacodynamic relationship for ShK-186 in rats and monkeys. The pharmacokinetic profile of ShK-186 was evaluated with a validated high-performance liquid chromatography-tandem mass spectrometry method to measure the peptide's concentration in plasma. These results were compared with single-photon emission computed tomography/computed tomography data collected with an ¹¹¹In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugate of ShK-186 to assess whole-blood pharmacokinetic parameters as well as the peptide's absorption, distribution, and excretion. Analysis of these data support a model wherein ShK-186 is absorbed slowly from the injection site, resulting in blood concentrations above the Kv1.3 channel-blocking IC₅₀ value for up to 7 days in monkeys. Pharmacodynamic studies on human peripheral blood mononuclear cells showed that brief exposure to ShK-186 resulted in sustained suppression of cytokine responses and may contribute to prolonged drug effects. In delayed-type hypersensitivity, chronic relapsing-remitting experimental autoimmune encephalomyelitis, and pristane-induced arthritis rat models, a single dose of ShK-186 every 2 to 5 days was as effective as daily administration. ShK-186's slow distribution from the injection site and its long residence time on the Kv1.3 channel contribute to the prolonged therapeutic effect of ShK-186 in animal models of autoimmune disease.
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