Evidence map›Paper›PMID 39248322›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Optimizing Nav1.7-Targeted Analgesics: Revealing Off-Target Effects of Spider Venom-Derived Peptide Toxins and Engineering Strategies for Improvement.

Sen Luo, Xi Zhou, Meijing Wu, Gongxin Wang, Li Wang, Xujun Feng, Hang Wu, Ren Luo, Minjuan Lu, Junxian Ju and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Toxicology reports · 2025
    Article
  3. Discovery of Novel NaResearch (Washington, D.C.) · 2025
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Sen LuoThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Xi ZhouThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Meijing WuThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Gongxin WangHenan Academy of Innovations in Medical science, Institute of Electrophysiology, Zhengzhou, Henan, 450000, China.
Li WangThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Xujun FengThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Hang WuThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Ren LuoThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Minjuan LuThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Junxian JuThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Wenxing WangThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Lei YuanThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Xiaoqing LuoThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Dezheng PengKey Laboratory of Hunan Province for Advanced Carbon-based Functional Materials, School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, 414006, China.
Li YangThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Qingfeng ZhangThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Minzhi ChenThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Songping LiangThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Xiuming DongDepartment of Research, Scope Research Institute of Electrophysiology, Kaifeng, 475004, China.
Guoliang HaoHenan Academy of Innovations in Medical science, Institute of Electrophysiology, Zhengzhou, Henan, 450000, China.
Yunxiao ZhangKey Laboratory of Hunan Province for Advanced Carbon-based Functional Materials, School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, 414006, China.
Zhonghua LiuThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.ORCID 0000-0001-8497-6702

Funding

The Hunan Provincial Natural Science Foundation of China 2020JJ5359：2022JJ40159The National Natural Science Foundation of China 31770832The National Natural Science Foundation of China 31800655The National Natural Science Foundation of China 31872718The National Natural Science Foundation of China 31900906The National Natural Science Foundation of China 32071262The National Natural Science Foundation of China 32271329The National Natural Science Foundation of China 32371322The National Natural Science Foundation of China 32371327The open research fund of Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control HPKL2023030The Science and Technology Innovation Program of Hunan Province 2020RC4023The Science and Technology Innovation Program of Hunan Province 2021RC3092The Science and Technology Innovation Program of Hunan Province 22B0069The Scientific Research Program of FuRong Laboratory 2023SK2096
6 · The paper itself

Abstract

The inhibition of Nav1.7 is a promising strategy for the development of analgesic treatments. Spider venom-derived peptide toxins are recognized as significant sources of Nav1.7 inhibitors. However, their development has been impeded by limited selectivity. In this study, eight peptide toxins from three distinct spider venom Nav channel families demonstrated robust inhibition of hNav1.7, rKv4.2, and rKv4.3 (rKv4.2/4.3) currents, exhibiting a similar mode of action. The analysis of structure and function relationship revealed a significant overlap in the pharmacophore responsible for inhibiting hNav1.7 and rKv4.2 by HNTX-III, although Lys25 seems to play a more pivotal role in the inhibition of rKv4.2/4.3. Pharmacophore-guided rational design is employed for the development of an mGpTx1 analogue, mGpTx1-SA, which retains its inhibition of hNav1.7 while significantly reducing its inhibition of rKv4.2/4.3 and eliminating cardiotoxicity. Moreover, mGpTx1-SA demonstrates potent analgesic effects in both inflammatory and neuropathic pain models, accompanied by an improved in vivo safety profile. The results suggest that off-target inhibition of rKv4.2/4.3 by specific spider peptide toxins targeting hNav1.7 may arise from a conserved binding motif. This insight promises to facilitate the design of hNav1.7-specific analgesics, aimed at minimizing rKv4.2/4.3 inhibition and associated toxicity, thereby enhancing their suitability for therapeutic applications.

Indexed as

AnalgesicsDisease Models, AnimalNAV1.7 Voltage-Gated Sodium ChannelSpider VenomsAnimalsHumansMicePeptidesAnalgesicsNAV1.7 Voltage-Gated Sodium ChannelPeptidesSCN9A protein, humanSpider VenomsanalgesicKv4.2 and Kv4.3Nav1.7off‐targetspider venom‐derived peptide toxins

Identifiers

PMID39248322
PMCPMC11558128

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.