Evidence map›Paper›PMID 28698055›Full record

ArticleToxicon : official journal of the International Society on Toxinology2017

Small molecule metalloprotease inhibitor with in vitro, ex vivo and in vivo efficacy against botulinum neurotoxin serotype A.

Alan R Jacobson, Michael Adler, Nicholas R Silvaggi, Karen N Allen, Genessa M Smith, Ross A Fredenburg, Ross L Stein, Jong-Beak Park, Xiaochuan Feng, Charles B Shoemaker and 7 more

Open access · greenAbstract read
In one paragraph

Article in Toxicon : official journal of the International Society on Toxinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Botulinum neurotoxin: from molecular pathogenesis to emerging countermeasures.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
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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

17 authors at 5 institutions in 2 countries.

Alan R JacobsonAbsolute Science, Inc., Denver, CO, 80222, United States.
Michael AdlerNeuroscience Branch, Medical Toxicology Division, USAMRICD, APG, MD, 21010, United States. Electronic address: michael.adler2.civ@mail.mil.
Nicholas R SilvaggiDepartment of Chemistry, Boston University, Boston, MA, 02215, United States.
Karen N AllenDepartment of Chemistry, Boston University, Boston, MA, 02215, United States.
Genessa M SmithAbsolute Science, Inc., Denver, CO, 80222, United States.
Ross A FredenburgCenter for Neurologic Diseases, Brigham & Women's Hospital and Harvard Medical School, Cambridge, MA, 02139, United States.
Ross L SteinLaboratory for Drug Discovery in Neurodegeneration, Brigham & Women's Hospital and Harvard Medical School, Cambridge, MA, 02139, United States.
Jong-Beak ParkDivision of Infectious Diseases, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, 01536, United States.
Xiaochuan FengDivision of Infectious Diseases, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, 01536, United States.
Charles B ShoemakerDivision of Infectious Diseases, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, 01536, United States.
Sharad S DeshpandeNeuroscience Branch, Medical Toxicology Division, USAMRICD, APG, MD, 21010, United States.
Michael C GoodnoughMetabiologics, Inc., Madison, WI, 53719, United States.
Carl J MalizioMetabiologics, Inc., Madison, WI, 53719, United States.
Eric A JohnsonDepartment of Bacteriology, University of Wisconsin at Madison, Madison, WI, 53706, United States.
Sabine PellettDepartment of Bacteriology, University of Wisconsin at Madison, Madison, WI, 53706, United States.
William H TeppDepartment of Bacteriology, University of Wisconsin at Madison, Madison, WI, 53706, United States.
Saul TziporiDivision of Infectious Diseases, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, 01536, United States.
Tufts University · USUniversity of Wisconsin–Madison · USBoston University · USBrigham and Women's Hospital · USSt Michael's Hospital · GB

Funding

GENETICS AND ROLE OF ALGINATE IN P. AERUGINOSA INFECTIONR29AI030050 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GOLDBERG, JOANNA B. · 1991 to 1995
–
NIAID NIH HHS N01 AI030050
6 · The paper itself

Abstract

Botulinum neurotoxins (BoNTs) are the most toxic substances known to mankind and are the causative agents of the neuroparalytic disease botulism. Their ease of production and extreme toxicity have caused these neurotoxins to be classified as Tier 1 bioterrorist threat agents and have led to a sustained effort to develop countermeasures to treat intoxication in case of a bioterrorist attack. While timely administration of an approved antitoxin is effective in reducing the severity of botulism, reversing intoxication requires different strategies. In the present study, we evaluated ABS 252 and other mercaptoacetamide small molecule active-site inhibitors of BoNT/A light chain using an integrated multi-assay approach. ABS 252 showed inhibitory activity in enzymatic, cell-based and muscle activity assays, and importantly, produced a marked delay in time-to-death in mice. The results suggest that a multi-assay approach is an effective strategy for discovery of potential BoNT therapeutic candidates.

Indexed as

AnimalsBotulinum Toxins, Type ACells, CulturedCrystallography, X-RayDrug DiscoveryMaleMetalloproteasesMiceMuscle ContractionMusclesNeurotoxinsProtease InhibitorsRats, Sprague-DawleyBotulinum Toxins, Type AMetalloproteasesNeurotoxinsProtease InhibitorsBotulinum neurotoxinBotulinum toxinBotulismMercaptoacetamideMetalloprotease inhibitorSNAP-25SNARE proteinX-ray crystallography

Identifiers

PMID28698055
PMCPMC5694348
OpenAlexW2732120602

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.