Evidence map›Paper›PMID 29198864›Full record

ArticleBioorganic & medicinal chemistry letters2018

Small molecule inhibitors of anthrax edema factor.

Guan-Sheng Jiao, Seongjin Kim, Mahtab Moayeri, April Thai, Lynne Cregar-Hernandez, Linda McKasson, Sean O'Malley, Stephen H Leppla, Alan T Johnson

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2018. 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
0.1field-weighted citation impact, top 48% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
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

9 authors at 2 institutions in 1 country.

Guan-Sheng JiaoHawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA.
Seongjin KimHawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA.
Mahtab MoayeriLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
April ThaiHawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA.
Lynne Cregar-HernandezHawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA.
Linda McKassonHawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA.
Sean O'MalleyHawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA.
Stephen H LepplaLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Alan T JohnsonHawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA. Electronic address: Johnson@hibiotech.com.
Hawaii Biotech (United States) · USNational Institute of Allergy and Infectious Diseases · US

Funding

Vaccines and Therapeutics for AnthraxZIAAI000929 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LEPPLA, STEPHEN · 2009 to 2025
$15.9M
Vaccines and Therapeutics for AnthraxZ01AI000929 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI LEPPLA, STEPHEN H · 2003 to 2008
$6.7M
Intramural NIH HHS Z01 AI000929
6 · The paper itself

Abstract

Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production.

Indexed as

AnimalsAnthraxAntigens, BacterialBacillus anthracisBacterial ToxinsCyclic AMPDose-Response Relationship, DrugHumansMiceMolecular StructureProtein KinasesRAW 264.7 CellsSmall Molecule LibrariesStructure-Activity Relationshipanthrax toxinAntigens, BacterialBacterial ToxinsCyclic AMPProtein KinasesSmall Molecule LibrariesAnthraxCovalent inhibitorEdema factor

Identifiers

PMID29198864
PMCPMC5875723
OpenAlexW2770937141

What OpenQuestion holds

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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.