Evidence map›Paper›PMID 37149747›Full record

ArticleImmunology and cell biology2023

Chemical inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4

Ana C Azevedo-Pouly, Lauren E Appell, Lyle Burdine, Lora J Rogers, Lauren C Morehead, Daniel Fil, Melanie Barker, Randall R Rainwater, Zachary J Waldrip, Brian Koss and 1 more

Open access · greenAbstract read
In one paragraph

Article in Immunology and cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024
    Review
  6. 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

11 authors at 2 institutions in 1 country.

Ana C Azevedo-PoulyDivision of Surgical Research, Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.ORCID 0000-0001-8308-9271
Lauren E AppellDepartment of Pediatric Hematology and Oncology, Arkansas Children's Hospital, Little Rock, AR, USA.
Lyle BurdineDivision of Surgical Research, Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Lora J RogersDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Lauren C MoreheadDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Daniel FilDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Melanie BarkerDivision of Surgical Research, Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Randall R RainwaterDivision of Surgical Research, Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Zachary J WaldripDivision of Surgical Research, Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Brian KossDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Marie Schluterman BurdineDivision of Surgical Research, Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Arkansas Children's Hospital · USUniversity of Arkansas for Medical Sciences · US

Funding

Translational Regulation in Normal Erythropoiesis and Diamond Blackfan AnemiaP20GM121293 · NIGMS · ARKANSAS CHILDREN'S HOSPITAL RES INST · PI Joseph Lee Alge · 2017 to 2026
$27.6M
Discovering T cell proteome turnover dynamics to overcome the solid tumor microenvironmentDP5OD031863 · OD · UNIV OF ARKANSAS FOR MED SCIS · PI KOSS, BRIAN · 2021 to 2025
$1.9M
DNA-PKcs Regulation of LAT-Mediated Early TCR Signaling in CD4+ and CD8+ T CellsR21AI173759 · NIAID · ARKANSAS CHILDREN'S HOSPITAL RES INST · PI BURDINE, MARIE SCHLUTERMAN, KOSS, BRIAN · 2023 to 2024
$424k
NIAID NIH HHS R21 AI173759NIGMS NIH HHS P20 GM121293NIH HHS DP5 OD031863
6 · The paper itself

Abstract

Modulation of T cell activity is an effective strategy for the treatment of autoimmune diseases, immune-related disorders and cancer. This highlights a critical need for the identification of proteins that regulate T cell function. The kinase DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is emerging as a potent regulator of the immune system, spurring interest in its use as a therapeutic target. In murine models of immune-related diseases including asthma and rheumatoid arthritis, treatment with small-molecule DNA-PKcs inhibitors decreased the disease severity. Additionally, DNA-PKcs inhibitors reduced T cell-mediated graft rejection in a murine allogenic skin graft model. These in vivo studies suggest the use of DNA-PKcs inhibitors as immunotherapy for autoimmune and T cell-mediated disorders. In this study, we sought to characterize further the effects of DNA-PKcs inhibitors on T cells to better understand their clinical potential. We determined that inhibition of DNA-PKcs using inhibitor NU7441 and the inhibitors currently in clinical trials for cancer therapy, M3184 and AZD7648, abrogated the activation of murine and human CD4

Indexed as

Antineoplastic AgentsDNA-Activated Protein KinaseAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDNAHumansMiceAntineoplastic AgentsDNADNA-Activated Protein KinaseCD4+ helper T cellsCD8+ effector T cellscytotoxicityDNA dependent protein kinase catalytic subunitNU7441T cell activationOTISIINFEKL-MC38T cell metabolism

Identifiers

PMID37149747
PMCPMC10527493
OpenAlexW4375846153

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.