STING

STING

STING (Stimulator of Interferon Genes) is an endoplasmic reticulum-associated transmembrane protein that is essential for activation of the innate immune system in response to the sensing of cytosolic DNA.^1,2,3 It controls the transcription of numerous defenses including type I interferons and pro-inflammatory cytokines. In addition to detecting pathogenic DNA, it may react to self-DNA resulting in autoinflammatory diseases and inflammation-associated cancers.^4,5 Conversely, STING agonists are potential cancer immunotherapy enhancers.⁶

DMXAA - 10-2676

STING (Stimulator of Interferon Genes) agonist selective for mouse STING. ^7,8 Intratumoural administration of DMXAA resulted in tumour regression and complete rejection in mouse xenografts. ⁹

2', 3' -cGAMP - 10-1639

Endogenous STING (Stimulator of Interferon Genes) agonist. ¹⁰ Produced from ATP and GTP via the action of cGMP-AMP synthase (cGAS) which acts as a cytosolic DNA sensor. ^{11, 12} Induces autophagy which is a mechanism for clearance of DNA and viruses in the cytosol. ¹³ DNA damage stimulates 2', 3'- cGAMP which stimulates an inflammatory response. ¹⁴

H-151 - 10-4132

H-151 is an inhibitor of the signalling molecule STING in mouse and human cells. ¹⁵ It covalently binds to Cys91 of STING preventing activation via blockade of palmitoylation at Cys91. It reduced systemic cytokine response in mice treated with the STING agonist 10-carboxymethyl-9-acridanone and showed efficacy in Trex^-/- mice.

C-176 - 10-4130

C-176 is an inhibitor of STING in mouse cells. ¹⁵ Treatment of Trex^-/-mice with C-176 resulted in a significant reduction in serum levels of Type I Interferons and amelioration of systemic inflammation.

C-178 - 10-4131

C-178 is an inhibitor of the signalling molecule STING in mouse cells. ¹⁵

References

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