Table 1 Overview of cGAS-STING signaling pathway inhibitors.
Target | Inhibitor(s) | Molecular mechanism | Models | Reference |
|---|---|---|---|---|
cGAS | Antimalarial drugs (primaquine, chloroquine, hydroxychloroquine, etc.) | Disrupting cGAS/DNA binding complex interface via interacting with DNA | THP1 cells | [86] |
cGAS | RU.521 | Exerting an inhibitory effect on ATP and GTP catalytic active sites on cGAS, affecting the production of cGAMP | RAW macrophage cells | |
cGAS | Suramin, oligodeoxynucleotides A151, and X6 | Competitive inhibition of DNA binding sites of cGAS. | Human monocytes and THP1 cells | |
cGAS | Aspirin | Acetylating cGAS at three lysine residues and blocking the activity of cGAS | THP-1, human PBMCs, and mouse bone marrow cells | [91] |
cGAS | EGCG | EGCG disrupted existing G3BP1-cGAS complexes and inhibited the activation of cGAS induced by DNAs, inhibiting the generation of IFN due to DNA. | U937 cells and Trex1 − /− bone marrow cells | [92] |
STING | Astin C | Binding to the C-terminal activation pocket of STING and competitively displacing CDNs to block the recruitment of IRF3 onto the STING signalosome. | HEK293 cells | [93] |
STING | Nitrofuran derivatives (C-176, C-178, C-170, C-171, and H-151) | Suppressing the STING clustering caused by palmitoylation by modifying the Cys91 residue in a covalent way. | HEK293T cells | [95] |
STING | Tetradroisoquinolone acetic acid | Displacing cGAMP from its binding site on STING | Not mentioned | [96] |
STING | Amlexanox | Blocking the full activation of STING by inhibiting the STING at Ser366 induced by TBK1 | Mouse lungs | |
Cytosolic DNA | Metformin and Rapamycin | Autophagy can decrease the load of cytoplasmic DNA | Nucleus pulposus cells and NIH3T3 cells and MRC-5 cells |
