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STING

The cGAS-STING pathway is a cellular DNA sensor that’s involved in innate immunity. It senses the DNA of invading microorganisms and releases a messenger molecule (cGAMP) which stimulates the cell to respond.  One practical application is in cancer immunotherapy.

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

  1. Ishikawa et al. (2008) Nature 455 674
  2. Ishikawa et al. (2009) Nature 461 788
  3. Burdette et al. (2011) Nature 478 515
  4. Ahn and Barber (2014) Curr.Opin.Immunol. 31 121
  5. Ablasser et al. (2014) J.Immunol. 192 5993
  6. Woo et al. (2015) Trends Immunol. 36 250
  7. Prantner et al. (2012), J.Biol.Chem. 287 39776
  8. Conlon et al. (2013), J.Immunol. 190 5216
  9. Corrales et al. (2015), Cell Rep. 11 1018
  10. Zhang et al. (2015), Mol.Cell, 51 226
  11. Wu et al. (2013), Science 339 826
  12. Sun et al. (2013), Science.339 786
  13. Gui et al. (2019), Nature. 567 262
  14. Li and Chen (2018), J.Exp.Med. 215 1287
  15. Haag et al. (2018), Nature 559 269