Evidence map›Paper›PMID 19876397›Full record

ArticlePloS one2009

Versatile assays for high throughput screening for activators or inhibitors of intracellular proteases and their cellular regulators.

Hideki Hayashi, Michael Cuddy, Vincent Chih-Wen Shu, Kenneth W Yip, Charitha Madiraju, Paul Diaz, Toshifumi Matsuyama, Muneshige Kaibara, Kohtaro Taniyama, Stefan Vasile and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. 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
0.4field-weighted citation impact, top 37% 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, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. ATP-Binding and Hydrolysis in Inflammasome Activation.Molecules (Basel, Switzerland) · 2020
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. 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

12 authors at 3 institutions in 2 countries.

Hideki HayashiBurnham Institute for Medical Research, La Jolla, California, USA.
Michael Cuddy
Vincent Chih-Wen Shu
Kenneth W Yip
Charitha Madiraju
Paul Diaz
Toshifumi Matsuyama
Muneshige Kaibara
Kohtaro Taniyama
Stefan Vasile
Eduard Sergienko
John C Reed
Institute for Medical Research · USNagasaki University · JPSanford Burnham Prebys Medical Discovery Institute · US

Funding

Countermeasures for Bioterroism Targeting Cellular Host FactorsU01AI078048 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI REED, JOHN C · 2008 to 2012
$4.0M
Yeast-based HTS Assay Technologies for ProteasesR01AI082629 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI REED, JOHN C · 2009 to 2012
$1.8M
NIAID NIH HHS R01 AI082629NIAID NIH HHS R01-AI082629NIAID NIH HHS U01 AI078048NIAID NIH HHS U01-AI078048
6 · The paper itself

Abstract

backgroundIntracellular proteases constitute a class of promising drug discovery targets. Methods for high throughput screening against these targets are generally limited to in vitro biochemical assays that can suffer many technical limitations, as well as failing to capture the biological context of proteases within the cellular pathways that lead to their activation. METHODS #ENTITYSTARTX00026;

findingsWe describe here a versatile system for reconstituting protease activation networks in yeast and assaying the activity of these pathways using a cleavable transcription factor substrate in conjunction with reporter gene read-outs. The utility of these versatile assay components and their application for screening strategies was validated for all ten human Caspases, a family of intracellular proteases involved in cell death and inflammation, including implementation of assays for high throughput screening (HTS) of chemical libraries and functional screening of cDNA libraries. The versatility of the technology was also demonstrated for human autophagins, cysteine proteases involved in autophagy.

conclusionsAltogether, the yeast-based systems described here for monitoring activity of ectopically expressed mammalian proteases provide a fascile platform for functional genomics and chemical library screening.

Indexed as

Small Molecule LibrariesCaspase 8Chemistry, PharmaceuticalCombinatorial Chemistry TechniquesDrug DesignDrug Evaluation, PreclinicalGene LibraryGenes, ReporterHumansInflammationPeptide HydrolasesPeptide LibraryProtease InhibitorsStructure-Activity RelationshipTranscription, GeneticCaspase 8Peptide HydrolasesPeptide LibraryProtease InhibitorsSmall Molecule Libraries

Identifiers

PMID19876397
PMCPMC2764853
OpenAlexW2011717325

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.