ArticleScientific reports2018
Physical basis of specificity and delayed binding of a subtype selective sodium channel inhibitor.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 8 citations in OpenAlex.
- Repurposing FDA-Approved Drugs as Nav1.7 Channel Modulators: An Integrated Structure-Based Virtual Screening and Molecular Dynamics Study.International journal of molecular sciences · 2026Article
- Lacosamide Inhibition of NaFrontiers in pharmacology · 2021Article
- Protonation state of inhibitors determines interaction sites within voltage-gated sodium channels.Proceedings of the National Academy of Sciences of the United States of America · 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
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nerve and muscle signalling is controlled by voltage-gated sodium (Nav) channels which are the targets of local anesthetics, anti-epileptics and anti-arrythmics. Current medications do not selectively target specific types of Nav found in the body, but compounds that do so have the potential to be breakthrough treatments for chronic pain, epilepsy and other neuronal disorders. We use long computer simulations totaling more than 26 μs to show how a promising lead compound can target one Nav implicated in pain perception and specific channels found in bacteria, and accurately predict the affinity of the compound to different channel types. Most importantly, we provide two explanations for the slow kinetics of this class of compound that limits their therapeutic utility. Firstly, the negative charge on the compound is essential for high affinity binding but is also responsible for energetic barriers that slow binding. Secondly, the compound has to undergo a conformational reorientation during the binding process. This knowledge aids the design of compounds affecting specific eukaryotic and bacterial channels and suggests routes for future drug development.
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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.