Evidence map›Paper›PMID 37939709›Full record

ArticleCell chemical biology2023

AGC kinase inhibitors regulate STING signaling through SGK-dependent and SGK-independent mechanisms.

Johnny Castillo Cabrera, Hong Dang, Adam Graves, Zhigang Zhang, Jose Torres-Castillo, Kelin Li, Zayna King, Pengda Liu, Jeff Aubé, James E Bear and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Classification and regulatory interactions of key transcription factors in COVID-19.Frontiers in cellular and infection microbiology · 2025
    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

13 authors at 1 institution in 1 country.

Johnny Castillo CabreraPathobiology and Translational Sciences Graduate Program, Department of Pathology and Laboratory Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hong DangDivision of Pulmonary Diseases and Critical Care Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Marsico Lung Institute, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Adam GravesLineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Zhigang ZhangLineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jose Torres-CastilloDivision of Pulmonary Diseases and Critical Care Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Marsico Lung Institute, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kelin LiDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Zayna KingDepartment of Cell Biology and Physiology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Pengda LiuLineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Biochemistry and Biophysics, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jeff AubéDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
James E BearLineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Cell Biology and Physiology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Blossom DamaniaLineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Robert S HaganDivision of Pulmonary Diseases and Critical Care Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Marsico Lung Institute, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: robhagan@email.unc.edu.
Albert S BaldwinLineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: albert_baldwin@med.unc.edu.
University of North Carolina at Chapel Hill · US

Funding

IKK/NF-kappaB Signaling in Cancer: Therapy, Resistance, and Tumor Initiating CellsR35CA197684 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 2016 to 2022
$5.8M
Systematic Analysis of the Actin Cytoskeleton and Directed Cell MigrationR35GM130312 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JAMES E BEAR · 2019 to 2026
$4.8M
Macrophage and monocyte TBK1 function in host defense against influenzaK08HL143271 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAGAN, ROBERT STEWART · 2019 to 2021
$535k
Functions of TBK1 in neutrophils during bacterial pneumoniaR03HL155249 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAGAN, ROBERT STEWART · 2021 to 2022
$156k
NCI NIH HHS R35 CA197684NHLBI NIH HHS K08 HL143271NHLBI NIH HHS R03 HL155249NIGMS NIH HHS R35 GM130312
6 · The paper itself

Abstract

Type 1 IFN expression is critical in the innate immune response, but aberrant expression is associated with autoimmunity and cancer. Here, we identify N-[4-(1H46 pyrazolo[3,4-b] pyrazin-6-yl)-phenyl]-sulfonamide (Sanofi-14h), a compound with preference for inhibition of the AGC family kinase SGK3, as an inhibitor of Ifnb1 gene expression in response to STING stimulation of macrophages. Sanofi-14h abrogated SGK activity and also impaired activation of the critical TBK1/IRF3 pathway downstream of STING activation, blocking interaction of STING with TBK1. Deletion of SGK1/3 in a macrophage cell line did not block TBK1/IRF3 activation but decreased expression of transcription factors, such as IRF7 and STAT1, required for the innate immune response. Other AGC kinase inhibitors blocked TBK1 and IRF3 activation suggesting common action on a critical regulatory node in the STING pathway. These studies reveal both SGK-dependent and SGK-independent mechanisms in the innate immune response and indicate an approach to block aberrant Ifnb1 expression.

Indexed as

Immunity, InnateMembrane ProteinsProtein Serine-Threonine KinasesAnimalsMicePhosphorylationRAW 264.7 CellsSerum-Glucocorticoid Regulated KinasesSignal TransductionSTING ProteinMembrane ProteinsProtein Serine-Threonine KinasesSerum-Glucocorticoid Regulated KinasesSgk3 protein, mouseSting1 protein, mouseSTING ProteinAGC kinasesdouble strand DNA viral responseinnate immunityinterferoninterferon regulatory factorIRFmacrophagesSanofi-14hserum and glucocorticoid kinaseSGKstimulator of interferon genesSTINGtank binding kinaseTBK1

Identifiers

PMID37939709
PMCPMC10842197
OpenAlexW4388453731

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.