ArticleMarine drugs2015
Development of highly selective Kv1.3-blocking peptides based on the sea anemone peptide ShK.
Article in Marine drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 68 citations in OpenAlex.
- Kv1.3 Channel inhibition by nanoformulated MeuKTx as a therapeutic strategy in breast cancer.Scientific reports · 2026Article
- Limosilactobacillus reuteri enables oral-to-systemic absorption of iberiotoxin for treatment of collagen-induced arthritis in rats.Microbial cell factories · 2025Article
- Anthozoan Chemical Defenses: Integrating Compounds, Enzymatic Activities, and Omics-Based Discoveries.International journal of molecular sciences · 2025Review
- Kv1.3 Ion Channels Mediate Electrical Stimulation-Induced Collagen Expression in Human Dermal Fibroblasts.Cosmetics · 2025Article
- Diversity analysis of sea anemone peptide toxins in different tissues of Heteractis crispa based on transcriptomics.Scientific reports · 2024Article
- Article
- Structure of the voltage-gated potassium channel KChannels (Austin, Tex.) · 2023Review
- Cyclic Peptides in Pipeline: What Future for These Great Molecules?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Genomic, functional and structural analyses elucidate evolutionary innovation within the sea anemone 8 toxin family.BMC biology · 2023Article
- 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
- Cm28, a scorpion toxin having a unique primary structure, inhibits KV1.2 and KV1.3 with high affinity.The Journal of general physiology · 2022Article
- Synthetic hookworm-derived peptides are potent modulators of primary human immune cell function that protect against experimental colitis in vivo.The Journal of biological chemistry · 2021Article
- Optimization ofFrontiers in pharmacology · 2021Article
- Engineering of a Spider PeptideFrontiers in molecular biosciences · 2021Article
- Proteomic Analysis of the Venom of JellyfishesMarine drugs · 2020Article
- Article
- Phosphonopeptides containing free phosphonic groups: recent advances.RSC advances · 2020Review
- Conformational exchange in the potassium channel blocker ShK.Scientific reports · 2019Article
- A Recurrent Motif: Diversity and Evolution of ShKT Domain Containing Proteins in the Vampire SnailToxins · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
ShK, from the sea anemone Stichodactyla helianthus, is a 35-residue disulfide-rich peptide that blocks the voltage-gated potassium channel Kv1.3 at ca. 10 pM and the related channel Kv1.1 at ca. 16 pM. We developed an analog of this peptide, ShK-186, which is currently in Phase 1b-2a clinical trials for the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. While ShK-186 displays a >100-fold improvement in selectivity for Kv1.3 over Kv1.1 compared with ShK, there is considerable interest in developing peptides with an even greater selectivity ratio. In this report, we describe several variants of ShK that incorporate p-phophono-phenylalanine at the N-terminus coupled with internal substitutions at Gln16 and Met21. In addition, we also explored the combinatorial effects of these internal substitutions with an alanine extension at the C-terminus. Their selectivity was determined by patch-clamp electrophysiology on Kv1.3 and Kv1.1 channels stably expressed in mouse fibroblasts. The peptides with an alanine extension blocked Kv1.3 at low pM concentrations and exhibited up to 2250-fold selectivity for Kv1.3 over Kv1.1. Analogs that incorporates p-phosphono-phenylalanine at the N-terminus blocked Kv1.3 with IC50s in the low pM range and did not affect Kv1.1 at concentrations up to 100 nM, displaying a selectivity enhancement of >10,000-fold for Kv1.3 over Kv1.1. Other potentially important Kv channels such as Kv1.4 and Kv1.6 were only partially blocked at 100 nM concentrations of each of the ShK analogs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.