Table 1.
An overview of STING inhibitors.
| Inhibitor [Ref] |
Binding Sites | Molecular Mechanism |
Biological Activity |
|---|---|---|---|
| Nitro-fatty acid Derivatives [102] |
C88, C91 at palmitoylation site and H16 in N-terminus | Covalently bind to the STING cysteines residues, block STING palmitoylation and inhibit STING activation | N.D. |
| C-176/178/170 and H-151 [103] |
C91 at palmitoylation site | IC50 (H-151) = 134.4 nM (HFFs cells) |
|
| BPK-21/25 [104] |
C91 at palmitoylation site | ISRE-Luc activity (BPK-25) = 3.2 μM (THP1 cells) | |
| Astin C [21] |
CDN binding site | Compete with cGAMP for the CDNs binding pocket and inhibit STING activation | IC50 = 3.42 ± 0.13 μM (MEFs cells) |
| Compound 18 [105] |
CDN binding site | IC50 = 68 nM (STINGHAQ); IC50 = 11 μM (THP1 cells) |
|
| SN-011 [106] |
CDN binding site | IC50 = 502.8 nM (HFFs cells) | |
| Palbociclib [107] |
CDN binding site | Interact with STING CTD and block STING dimerization | IC50 = 0.81 ± 0.93 μM (HEK293 cells) |
| Compound 30 [108] |
CDN binding site | Undetermined | IC50 = 1.15 μM (RAW264.7 cells) |
| 6,5-heterocyclic derivatives | Unknown | Undetermined | IC50 ranges from 30 μM to less than 10 nM |
| SP23 [109] |
Palmitoylation site | Promote the degradation of STING via ubiquitin-proteasome pathway | DC50 = 3.2 μM (THP1 cells) |