Evidence map›Paper›PMID 27932698›Full record

ArticleSLAS discovery : advancing life sciences R & D2017

Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen.

Patrick R Visperas, Christopher G Wilson, Jonathan A Winger, Qingrong Yan, Kevin Lin, Michelle R Arkin, Arthur Weiss, John Kuriyan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in SLAS discovery : advancing life sciences R & D, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018
    Review
  9. Article
  10. 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

8 authors.

Patrick R Visperas1 Department of Molecular and Cell Biology and Department of Chemistry, California Institute of Quantitative Biosciences and Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
Christopher G Wilson3 Department of Pharmaceutical Chemistry, Small Molecule Discovery Center, University of California, San Francisco, CA, USA.
Jonathan A Winger1 Department of Molecular and Cell Biology and Department of Chemistry, California Institute of Quantitative Biosciences and Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
Qingrong Yan1 Department of Molecular and Cell Biology and Department of Chemistry, California Institute of Quantitative Biosciences and Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
Kevin Lin1 Department of Molecular and Cell Biology and Department of Chemistry, California Institute of Quantitative Biosciences and Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
Michelle R Arkin3 Department of Pharmaceutical Chemistry, Small Molecule Discovery Center, University of California, San Francisco, CA, USA.
Arthur Weiss4 Department of Medicine, Rosalind Russell and Ephrain P. Engleman Rheumatology Research Center for Arthritis and Howard Hughes Medical Institute, University of California, San Francisco, CA, USA.
John Kuriyan1 Department of Molecular and Cell Biology and Department of Chemistry, California Institute of Quantitative Biosciences and Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.

Funding

Understand the metabolic fitness of naïve T cellsP01AI091580 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ARTHUR WEISS · 2011 to 2026
$31.1M
An allosteric inhibitor of ZAP-70 as a novel therapeutic for autoimmune diseaseRC2AR058947 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEISS, ARTHUR · 2009 to 2010
$1.8M
ARRA NIH HHSNIAID NIH HHS P01 AI091580NIAMS NIH HHS RC2 AR058947
6 · The paper itself

Abstract

ZAP-70 is a critical molecule in the transduction of T cell antigen receptor signaling and the activation of T cells. Upon activation of the T cell antigen receptor, ZAP-70 is recruited to the intracellular ζ-chains of the T cell receptor, where ZAP-70 is activated and colocalized with its substrates. Inhibitors of ZAP-70 could potentially function as treatments for autoimmune diseases or organ transplantation. In this work, we present the design, optimization, and implementation of a screen for inhibitors that would disrupt the interaction between ZAP-70 and the T cell antigen receptor. The screen is based on a fluorescence polarization assay for peptide binding to ZAP-70.

Indexed as

High-Throughput Screening AssaysCell-Free SystemFluorescence PolarizationFluorescence Resonance Energy TransferGene ExpressionHumansImmunologic FactorsPeptidesPhosphorylationProtein BindingProtein Kinase InhibitorsReceptors, Antigen, T-CellRecombinant ProteinsSignal TransductionSmall Molecule LibrariesZAP-70 Protein-Tyrosine KinaseImmunologic FactorsPeptidesProtein Kinase InhibitorsReceptors, Antigen, T-CellRecombinant ProteinsSmall Molecule LibrariesZAP70 protein, humanZAP-70 Protein-Tyrosine Kinasecovalent inhibitorfluorescence polarization (FP)kinaseT celltime-resolved fluorescence resonance energy transfer (TR-FRET)ZAP-70

Identifiers

PMID27932698
PMCPMC5491343

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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.