Interrupting cyclic dinucleotide-cGAS-STING axis with small molecules

Herman O Sintim; Clinton G Mikek; Modi Wang; Moloud A Sooreshjani

doi:10.1039/c8md00555a

Interrupting cyclic dinucleotide-cGAS-STING axis with small molecules

Medchemcomm. 2019 Aug 15;10(12):1999-2023. doi: 10.1039/c8md00555a. eCollection 2019 Dec 1.

Authors

Herman O Sintim^{1

2

3}, Clinton G Mikek¹, Modi Wang¹, Moloud A Sooreshjani¹

Affiliations

¹ Department of Chemistry , Purdue University , 560 Oval Drive , West Lafayette , IN 47907 , USA . Email: hsintim@purdue.edu.
² Institute for Drug Discovery , Purdue University , 720 Clinic Drive , West Lafayette , IN 47907 , USA.
³ Purdue Institute of Inflammation and Infectious Diseases , Purdue University , West Lafayette , IN 47907 , USA.

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 are 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 the 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.

Publication types

Review