Evidence map›Paper›PMID 27062893›Full record

ArticleChemico-biological interactions2016

Probing the activity of a non-oxime reactivator for acetylcholinesterase inhibited by organophosphorus nerve agents.

C Linn Cadieux, Haoyu Wang, Yuchen Zhang, Jeffrey A Koenig, Tsung-Ming Shih, John McDonough, John Koh, Douglas Cerasoli

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemico-biological interactions, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
8.2field-weighted citation impact, top 4% of its field
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

11 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019
    Review
  10. Article
  11. 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

8 authors at 2 institutions in 1 country.

C Linn CadieuxResearch Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA. Electronic address: christena.l.cadieux.ctr@mail.mil.
Haoyu WangChemistry and Biochemistry Department, University of Delaware, Newark, DE 19716, USA.
Yuchen ZhangChemistry and Biochemistry Department, University of Delaware, Newark, DE 19716, USA.
Jeffrey A KoenigResearch Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
Tsung-Ming ShihResearch Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
John McDonoughResearch Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
John KohChemistry and Biochemistry Department, University of Delaware, Newark, DE 19716, USA.
Douglas CerasoliResearch Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
United States Army · USUniversity of Delaware · US

Funding

This renovation project will create over 1455 sq. ft. of state- of-the-art reseaP20GM104316 · NIGMS · UNIVERSITY OF DELAWARE · PI FOX, JOSEPH M · 2014 to 2024
$26.8M
NIGMS NIH HHS P20 GM104316
6 · The paper itself

Abstract

Currently fielded treatments for nerve agent intoxication include atropine, an acetylcholine receptor antagonist, and pralidoxime (2PAM), a small molecule reactivator of acetylcholinesterase (AChE). 2PAM reactivates nerve agent-inhibited AChE via direct nucleophilic attack by the oxime moiety on the phosphorus center of the bound nerve agent. Due to a permanently charged pyridinium motif, 2PAM is not thought to cross the blood brain barrier and therefore cannot act directly in the neuronal junctions of the brain. In this study, ADOC, a non-permanently charged, non-oxime molecule initially identified using pesticide-inhibited AChE, was characterized in vitro against nerve agent-inhibited recombinant human AChE. The inhibitory and reactivation potentials of ADOC were determined with native AChE and AChE inhibited with tabun, sarin, soman, cyclosarin, VX, or VR and then compared to those of 2PAM. Several structural analogs of ADOC were used to probe the reactivation mechanism of the molecule. Finally, guinea pigs were used to examine the protective efficacy of the compound after exposure to sarin. The results of both in vitro and in vivo testing will be useful in the design of future small molecule reactivators.

Indexed as

AcetylcholinesteraseAnimalsCholinesterase ReactivatorsErythrocytesGuinea PigsHalf-LifeHumansKineticsMaleNerve AgentsOrganophosphate PoisoningOrganophosphatesOximesPhenolsPralidoxime CompoundsRecombinant Proteins4-amino-2-((diethylamino)methyl)phenolAcetylcholinesteraseCholinesterase ReactivatorsNerve AgentsOrganophosphatesOximesPhenolspralidoximePralidoxime CompoundsRecombinant ProteinsSarinSomantabunAcetylcholinesteraseGuinea pigOrganophosphorus nerve agentOximePralidoximeReactivator

Identifiers

PMID27062893
PMCPMC11525883
OpenAlexW2315996261

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.