ArticleThe Journal of biological chemistry2016
Engineering Highly Potent and Selective Microproteins against Nav1.7 Sodium Channel for Treatment of Pain.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- A Systematic Review of Traditionally Used Herbs and Animal-Derived Products as Potential Analgesics.Current neuropharmacology · 2021Pooled it
- Structural basis for inhibition of the voltage-gated sodium channel NaThe Journal of biological chemistry · 2026Article
- Refining the NaFEBS letters · 2025Article
- Optimizing Nav1.7-Targeted Analgesics: Revealing Off-Target Effects of Spider Venom-Derived Peptide Toxins and Engineering Strategies for Improvement.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Lessons learned in translating pain knowledge into practice.Pain reports · 2023Article
- Article
- Structure-function and rational design of a spider toxin Ssp1a at human voltage-gated sodium channel subtypes.Frontiers in pharmacology · 2023Article
- General mechanism of spider toxin family I acting on sodium channel Nav1.7.Zoological research · 2022Article
- Druggability of Voltage-Gated Sodium Channels-Exploring Old and New Drug Receptor Sites.Frontiers in pharmacology · 2022Review
- Selective Targeting of Nav1.7 with Engineered Spider Venom-Based Peptides.Channels (Austin, Tex.) · 2021Review
- Engineering of a Spider PeptideFrontiers in molecular biosciences · 2021Article
- Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Status of peripheral sodium channel blockers for non-addictive pain treatment.Nature reviews. Neurology · 2020Review
- Article
- Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.Toxins · 2019Review
- Evaluation of the Spider (Toxins · 2019Article
- Physician's role in prescribing opioids in developing countries.BMJ case reports · 2019Article
- From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei.British journal of pharmacology · 2019Article
- Structure-Function and Therapeutic Potential of Spider Venom-Derived Cysteine Knot Peptides Targeting Sodium Channels.Frontiers in pharmacology · 2019Review
- Engineering Gain-of-Function Analogues of the Spider Venom Peptide HNTX-I, A Potent Blocker of the hNaToxins · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prominent role of voltage-gated sodium channel 1.7 (Nav1.7) in nociception was revealed by remarkable human clinical and genetic evidence. Development of potent and subtype-selective inhibitors of this ion channel is crucial for obtaining therapeutically useful analgesic compounds. Microproteins isolated from animal venoms have been identified as promising therapeutic leads for ion channels, because they naturally evolved to be potent ion channel blockers. Here, we report the engineering of highly potent and selective inhibitors of the Nav1.7 channel based on tarantula ceratotoxin-1 (CcoTx1). We utilized a combination of directed evolution, saturation mutagenesis, chemical modification, and rational drug design to obtain higher potency and selectivity to the Nav1.7 channel. The resulting microproteins are highly potent (IC50 to Nav1.7 of 2.5 nm) and selective. We achieved 80- and 20-fold selectivity over the closely related Nav1.2 and Nav1.6 channels, respectively, and the IC50 on skeletal (Nav1.4) and cardiac (Nav1.5) sodium channels is above 3000 nm The lead molecules have the potential for future clinical development as novel therapeutics in the treatment of pain.
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Registered trials
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.