G10 is a direct activator of human STING

The cGAS/STING pathway initiates an innate immune response when DNA is detected in the cytosol. DNA bound cGAS synthesizes cyclic dinucleotides which bind and activate the adaptor STING, leading to downstream secretion of Type I interferons and other pro-inflammatory NFκB pathway cytokines. In the m...

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Bibliographic Details
Published in:PloS one 2020-09, Vol.15 (9), p.e0237743-e0237743
Main Authors: Banerjee, Monali, Middya, Sandip, Shrivastava, Ritesh, Basu, Sourav, Ghosh, Rajib, Pryde, David C, Yadav, Dharmendra B, Surya, Arjun
Format: Article
Language:English
Subjects:
Agonists
Animals
Antigens
Biology and Life Sciences
Cellular signal transduction
Cytokines
Cytosol
Deoxyribonucleic acid
DNA
Endoplasmic reticulum
Endoplasmic Reticulum - metabolism
Engineering and Technology
Fibroblasts
Genes
Genetic aspects
Health aspects
HEK293 Cells
Humans
Identification and classification
Immune clearance
Immune response
Immune system
Inflammation
Innate immunity
Interferon
Interferon Regulatory Factor-3 - metabolism
Kinases
Ligands
Medicine and Health Sciences
Membrane proteins
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Methods
Mice
NF-κB protein
Phosphorylation
Physical Sciences
Plasmids
Protein Domains
Protein Stability
Proteins
Research and Analysis Methods
Signal Transduction
Signaling peptides and proteins
THP-1 Cells
Tumors
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Description
Summary:The cGAS/STING pathway initiates an innate immune response when DNA is detected in the cytosol. DNA bound cGAS synthesizes cyclic dinucleotides which bind and activate the adaptor STING, leading to downstream secretion of Type I interferons and other pro-inflammatory NFκB pathway cytokines. In the mouse, the STING driven innate immune response is central to immune based clearance of various tumors and this has triggered a significant effort focused on the discovery of human STING agonists for the treatment of cancer. This report uses an in vitro kinase assay to show that G10, a previously identified STING pathway activator is actually a weak but direct STING agonist and identifies other more potent leads.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0237743