The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway
Abstract
:1. Introduction
2. Structure and Signaling Pathway of STING
3. NAFL/NASH and STING
4. NASH-Associated HCC and STING
5. STING Inhibitors and Agonists
5.1. Covalent Inhibitors
5.2. Noncovalent Inhibitors
5.3. CDNs Agonists
5.4. Non-CDN Agonists
6. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Mechanism | Reference |
---|---|---|
Tetrahydroisoquinoline derivatives (Compound 18) | Target CBD binding pocket | [92] |
Astin C | Inhibits STING-IRF3 interaction via the binding of the C-terminal domain of STING | [30] |
SN-011 | Target cyclic dinucleotide binding pocket | [91] |
NO2-FAs | Suppresses STING palmitoylation | [93] |
C-176, C-178 | Suppresses murine STING palmitoylation | [29] |
C170, C-171 | Suppresses murine STING palmitoylation | |
H-151 | Suppresses human STING palmitoylation | |
Gelsevirine | Targeting STING for K48 ubiquitination and degradation | [94] |
Palbociclib | Directly targets STING Y167 | [31] |
Compound | Phase; Start Time; Notes | Reference/Clinical Trials ID |
---|---|---|
MK-1454 | Ⅰ (2017): Intratumoral(IT); solid tumors or lymphomas | NCT03010176; NCT04220866; [103,104] |
Ⅱ (2020): IT; HNSCC | ||
MK-2118 | Ⅰ (2017): IT/SQ; solid tumors or lymphomas | NCT03249792 |
BMS-986301 | Ⅰ (2019): IV; advanced solid cancers | NCT03956680 |
BI-STING (BI1387446) | Ⅰ (2020): IT; advanced solid cancers | NCT04147234 |
SB 11285 | Ⅰ (2019): IV; advanced solid tumors: melanoma, HNSCC, and solid tumor | NCT04096638 |
IMSA-101(GB492) | Ⅰ/Ⅱ (2019): IV; solid tumor | NCT04020185; CTR20211689 |
Ⅰ (2021): I.V.; adult advanced malignant tumor | ||
E7766 | Ⅰ (2020): IT; advanced solid tumors or lymphomas | NCT04144140; NCT04109092 |
Withdrawn (Ⅰ(2020): urinary bladder neoplasms) | ||
MIW815(ADU-S100) | Terminated: Ⅰ (2016): advanced/metastatic solid tumors or lymphomas | NCT02675439; NCT03172936; NCT03937141 |
Terminated: Ⅰ(2017): advanced/metastatic solid tumors or lymphomas) | ||
Terminated: Ⅱ (2019: head and neck cancer) | ||
Compound 3 | Preclinical: Support IV | [106] |
a-Mangostin | Preclinical | [114] |
GSK3745417 | Ⅰ (2019): IV; advanced solid tumors | NCT03843359 |
BMS-986301 | Ⅰ (2019): IT/IM; advanced solid cancers | NCT03956680 |
SYNB1891 | Ⅰ (2019): IT; metastatic solid neoplasm lymphoma | NCT04167137 |
TAK-676 | Ⅰ (2020): IV; advanced solid tumors | NCT04420884; NCT04879849; NCT04541108 |
Early phase Ⅰ (2021): solid tumor | ||
SNX281 | Ⅰ (2020): IV; solid tumors and lymphoma | NCT04609579 |
MSA-1 | Preclinical | No data |
MSA-2 | Preclinical: orally available; antitumor | |
SR-001 | Preclinical: pro-drug | [111,112] |
SR717 | Preclinical: The compound was modified from the structure of SR-012 and was combined with cGAMP at the same position on STING; it could induce the same conformational change of STING and had a stronger response when combined with STING | |
HG381 | Ⅰ (2021): advanced solid tumors | NCT04998422; CTR20211765; |
Ⅰ (2021): advanced solid tumors Report: colorectal cancer; a better efficacy than ADB-S100 | ||
KL340399 | IND (2022: NMPA): IV; advanced solid tumor | CXHL2200223; CXHL2200224 |
NOX-66 | Completed: Ⅰ/Ⅱ (2017): Cancer | NCT02941523; NCT04957290 |
Ⅰ/Ⅱ (2021): metastatic castration-resistant prostate cancer and other solid tumors | ||
PC7A | Preclinical; form biomolecular condensates; intratumoral administration | [113,115,116] |
IACS-8779 | Preclinical (2021); IT; Canine glioblastoma | [117] |
TAK-500 | Recruiting:Ⅰ(2022), IV, HCC/Pancreatic cancer | NCT05070247 |
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Lv, J.; Xing, C.; Chen, Y.; Bian, H.; Lv, N.; Wang, Z.; Liu, M.; Su, L. The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway. Pharmaceuticals 2022, 15, 1241. https://doi.org/10.3390/ph15101241
Lv J, Xing C, Chen Y, Bian H, Lv N, Wang Z, Liu M, Su L. The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway. Pharmaceuticals. 2022; 15(10):1241. https://doi.org/10.3390/ph15101241
Chicago/Turabian StyleLv, Juan, Chunlei Xing, Yuhong Chen, Huihui Bian, Nanning Lv, Zhibin Wang, Mingming Liu, and Li Su. 2022. "The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway" Pharmaceuticals 15, no. 10: 1241. https://doi.org/10.3390/ph15101241
APA StyleLv, J., Xing, C., Chen, Y., Bian, H., Lv, N., Wang, Z., Liu, M., & Su, L. (2022). The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway. Pharmaceuticals, 15(10), 1241. https://doi.org/10.3390/ph15101241