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Interrupting cyclic dinucleotide-cGAS-STING axis with small molecules

Abstract

The cyclic dinucleotide-cGAS-STING axis plays important roles in host immunity. Activation of this signaling pathway, via cytosolic sensing of bacterial-derived c-di-GMP/c-di-AMP or host-derived cGAMP, leads to the production of inflammatory interferons and cytokines that help resolve infection. Small molecule activators of the cGAS-STING axis have the potential to augment immune response against various pathogens or cancer. The aberrant activation of this pathway, due to gain-of-function mutations in any of the proteins that is part of the signaling axis, could lead to various autoimmune diseases. Inhibiting various nodes of the cGAS-STING axis could provide relief to patients with autoimmune diseases. Many excellent reviews on the cGAS-STING axis have been published recently, and these have mainly focused on the molecular details of cGAS-STING pathway. This review however focuses on small molecules that can be used to modulate various aspects of the cGAS-STING pathway, as well as other parallel inflammatory pathways.

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Publication details

The article was received on 09 Nov 2018, accepted on 13 Aug 2019 and first published on 15 Aug 2019


Article type: Review Article
DOI: 10.1039/C8MD00555A
Med. Chem. Commun., 2019, Accepted Manuscript

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    Interrupting cyclic dinucleotide-cGAS-STING axis with small molecules

    C. Mikek, M. Wang, M. A. Sooreshjani and H. O. Sintim, Med. Chem. Commun., 2019, Accepted Manuscript , DOI: 10.1039/C8MD00555A

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