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G10 is a direct activator of human STING.

ABSTRACT: 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 NF?B 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.

SUBMITTER: Banerjee M

PROVIDER: S-EPMC7482845 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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G10 is a direct activator of human STING.

Banerjee Monali M Middya Sandip S Shrivastava Ritesh R Basu Sourav S Ghosh Rajib R Pryde David C DC Yadav Dharmendra B DB Surya Arjun A

PloS one 20200910 9

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 th ...[more]

PMID: 32911484

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