Evidence map›Paper›PMID 23133670›Full record

ArticlePloS one2012

Identification of small molecules that suppress ricin-induced stress-activated signaling pathways.

Paul G Wahome, Sarita Ahlawat, Nicholas J Mantis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Targeting ricin to the ribosome.Toxicon : official journal of the International Society on Toxinology · 2013
    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

3 authors at 2 institutions in 1 country.

Paul G WahomeDivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Sarita Ahlawat
Nicholas J Mantis
Wadsworth Center · USNew York State Department of Health · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CUNNINGHAM, JAMES · 2003 to 2013
$113.7M
Small molecule inhibitors of ricin and shiga toxinsU01AI075509 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI ROBERTUS, JON D · 2007 to 2011
$3.1M
NIAID NIH HHS 5U01 AI075509NIAID NIH HHS U01 AI075509NIAID NIH HHS U54 AI057159
6 · The paper itself

Abstract

Ricin is a member of the ribosome-inactivating protein (RIP) family of plant and bacterial toxins. In this study we used a high-throughput, cell-based assay to screen more than 118,000 compounds from diverse chemical libraries for molecules that reduced ricin-induced cell death. We describe three compounds, PW66, PW69, and PW72 that at micromolar concentrations significantly delayed ricin-induced cell death. None of the compounds had any demonstrable effect on ricin's ability to arrest protein synthesis in cells or on ricin's enzymatic activity as assessed in vitro. Instead, all three compounds appear to function by blocking downstream stress-induced signaling pathways associated with the toxin-mediated apoptosis. PW66 virtually eliminated ricin-induced TNF-α secretion by J774A.1 macrophages and concomitantly blocked activation of the p38 MAPK and JNK signaling pathways. PW72 suppressed ricin-induced TNF-α secretion, but not p38 MAPK and JNK signaling. PW69 suppressed activity of the executioner caspases 3/7 in ricin toxin- and Shiga toxin 2-treated cells. While the actual molecular targets of the three compounds have yet to be identified, these data nevertheless underscore the potential of small molecules to down-regulate inflammatory signaling pathways associated with exposure to the RIP family of toxins.

Indexed as

AnimalsCaspase 3Caspase 7Cell DeathCell LineChemistry, PharmaceuticalDrug DesignHumansInflammationMacrophagesMicep38 Mitogen-Activated Protein KinasesProtein BiosynthesisRabbitsRibosomesRicinCaspase 3Caspase 7p38 Mitogen-Activated Protein KinasesRicin

Identifiers

PMID23133670
PMCPMC3486792
OpenAlexW2072143408

What OpenQuestion 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 OpenQuestion graph.