Potential Therapeutic Value of the STING Inhibitors
Abstract
:1. Introduction
2. The Structure and Location of STING
3. The Function of STING
4. Genotype
5. DNA Sensors Upstream of STING
6. The Regulation of the STING Pathway
7. STING Inhibitors
7.1. STING Inhibitors Targeting the Palmitoylation Site
7.2. STING Inhibitors Targeting CDN Binding Site
7.3. STING Inhibitor with an Unknown Site of Action
7.4. STING Protein Degraders
8. STING-Related Diseases
8.1. STING and Psoriasis
8.2. STING and Systemic Lupus Erythematosus
8.3. STING and Infectious Diseases
8.4. STING and SAVI
8.5. STING and CNS Diseases
8.6. STING and Inflammatory Bowel Disease
8.7. STING and NAFLD
8.8. STING and Diabetic Complications
8.9. STING and Other Diseases
9. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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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) |
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Zhang, S.; Zheng, R.; Pan, Y.; Sun, H. Potential Therapeutic Value of the STING Inhibitors. Molecules 2023, 28, 3127. https://doi.org/10.3390/molecules28073127
Zhang S, Zheng R, Pan Y, Sun H. Potential Therapeutic Value of the STING Inhibitors. Molecules. 2023; 28(7):3127. https://doi.org/10.3390/molecules28073127
Chicago/Turabian StyleZhang, Shangran, Runan Zheng, Yanhong Pan, and Hongbin Sun. 2023. "Potential Therapeutic Value of the STING Inhibitors" Molecules 28, no. 7: 3127. https://doi.org/10.3390/molecules28073127