cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases
Yumin Wang,1,* Rui Yang,1,* Yuwei Cao,1,* Yulin Li,1 Yonglin Zhu,1 Zhe Zhang,1 Joshua S Fleishman,2 Jichao Chen,1 Mingchao Ding3 1Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medici...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-07-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/cgas-sting-targeting-offers-novel-therapeutic-opportunities-in-liver-d-peer-reviewed-fulltext-article-DDDT |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849702058156883968 |
|---|---|
| author | Wang Y Yang R Cao Y Li Y Zhu Y Zhang Z Fleishman JS Chen J Ding M |
| author_facet | Wang Y Yang R Cao Y Li Y Zhu Y Zhang Z Fleishman JS Chen J Ding M |
| author_sort | Wang Y |
| collection | DOAJ |
| description | Yumin Wang,1,* Rui Yang,1,* Yuwei Cao,1,* Yulin Li,1 Yonglin Zhu,1 Zhe Zhang,1 Joshua S Fleishman,2 Jichao Chen,1 Mingchao Ding3 1Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, 11439, USA; 3Department of Peripheral Vascular Intervention, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingchao Ding, Department of Peripheral Vascular Intervention, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People’s Republic of China, Email dmc_zxl@vip.sina.com Joshua S Fleishman, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, 11439, USA, Email joshua.fleishman18@my.stjohns.eduAbstract: Cyclic GMP/AMP (cGAMP) synthase (cGAS), coupled with the endoplasmic reticulum (ER)-anchored adaptor protein stimulator of interferon genes (STING), constitute key components of the type 1 interferon signaling network. cGAS detects both pathogen-derived DNA and aberrant cytosolic self-DNA, establishing the cGAS-STING pathway as a central player in autoimmune disorders, sterile inflammation, and senescence-related processes. However, sustained abnormal activation of this signaling axis is implicated in the pathogenesis of chronic inflammatory and autoimmune conditions. Recent studies have uncovered the pivotal role of cGAS-STING signaling in driving inflammation-associated pathologies, particularly hepatic disorders. Advances in understanding the molecular dynamics of this pathway have facilitated the development of targeted small-molecule inhibitors with therapeutic potential for cGAS-STING-driven liver diseases. In this review, we first delineate the core architecture of the cGAS-STING signaling cascade. Building on this framework, we analyze emerging evidence elucidating the mechanistic contributions of cGAS-STING activation to hepatic pathophysiology. Subsequently, we catalog pharmacologically active compounds capable of modulating this pathway in liver disease models. Finally, we critically evaluate current challenges in translating cGAS-STING-targeted therapies and propose strategic approaches to address these limitations. This synthesis underscores innovative therapeutic opportunities arising from precision modulation of the cGAS-STING axis in liver diseases.Keywords: cGAS, STING, antagonist, liver diseases |
| format | Article |
| id | doaj-art-5d2112e5baf5443bbea734cc22b18ecf |
| institution | DOAJ |
| issn | 1177-8881 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj-art-5d2112e5baf5443bbea734cc22b18ecf2025-08-20T03:17:46ZengDove Medical PressDrug Design, Development and Therapy1177-88812025-07-01Volume 19Issue 158355853104636cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver DiseasesWang Y0Yang R1Cao Y2Li Y3Zhu Y4Zhang Z5Fleishman JS6Chen J7Ding M8Department of Respiratory and Critical Care MedicineDepartment of Respiratory and Critical Care MedicineDepartment of Respiratory and Critical Care MedicineDepartment of Respiratory and Critical Care MedicineDepartment of Respiratory and Critical Care MedicineDepartment of Respiratory and Critical Care MedicineCollege of Pharmacy and Health SciencesDepartment of Respiratory and Critical Care MedicineDepartment of Peripheral Vascular InterventionYumin Wang,1,* Rui Yang,1,* Yuwei Cao,1,* Yulin Li,1 Yonglin Zhu,1 Zhe Zhang,1 Joshua S Fleishman,2 Jichao Chen,1 Mingchao Ding3 1Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, 11439, USA; 3Department of Peripheral Vascular Intervention, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingchao Ding, Department of Peripheral Vascular Intervention, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People’s Republic of China, Email dmc_zxl@vip.sina.com Joshua S Fleishman, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, 11439, USA, Email joshua.fleishman18@my.stjohns.eduAbstract: Cyclic GMP/AMP (cGAMP) synthase (cGAS), coupled with the endoplasmic reticulum (ER)-anchored adaptor protein stimulator of interferon genes (STING), constitute key components of the type 1 interferon signaling network. cGAS detects both pathogen-derived DNA and aberrant cytosolic self-DNA, establishing the cGAS-STING pathway as a central player in autoimmune disorders, sterile inflammation, and senescence-related processes. However, sustained abnormal activation of this signaling axis is implicated in the pathogenesis of chronic inflammatory and autoimmune conditions. Recent studies have uncovered the pivotal role of cGAS-STING signaling in driving inflammation-associated pathologies, particularly hepatic disorders. Advances in understanding the molecular dynamics of this pathway have facilitated the development of targeted small-molecule inhibitors with therapeutic potential for cGAS-STING-driven liver diseases. In this review, we first delineate the core architecture of the cGAS-STING signaling cascade. Building on this framework, we analyze emerging evidence elucidating the mechanistic contributions of cGAS-STING activation to hepatic pathophysiology. Subsequently, we catalog pharmacologically active compounds capable of modulating this pathway in liver disease models. Finally, we critically evaluate current challenges in translating cGAS-STING-targeted therapies and propose strategic approaches to address these limitations. This synthesis underscores innovative therapeutic opportunities arising from precision modulation of the cGAS-STING axis in liver diseases.Keywords: cGAS, STING, antagonist, liver diseaseshttps://www.dovepress.com/cgas-sting-targeting-offers-novel-therapeutic-opportunities-in-liver-d-peer-reviewed-fulltext-article-DDDTcGASSTINGAntagonistLiver Diseases |
| spellingShingle | Wang Y Yang R Cao Y Li Y Zhu Y Zhang Z Fleishman JS Chen J Ding M cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases Drug Design, Development and Therapy cGAS STING Antagonist Liver Diseases |
| title | cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases |
| title_full | cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases |
| title_fullStr | cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases |
| title_full_unstemmed | cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases |
| title_short | cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases |
| title_sort | cgas sting targeting offers novel therapeutic opportunities in liver diseases |
| topic | cGAS STING Antagonist Liver Diseases |
| url | https://www.dovepress.com/cgas-sting-targeting-offers-novel-therapeutic-opportunities-in-liver-d-peer-reviewed-fulltext-article-DDDT |
| work_keys_str_mv | AT wangy cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT yangr cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT caoy cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT liy cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT zhuy cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT zhangz cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT fleishmanjs cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT chenj cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases AT dingm cgasstingtargetingoffersnoveltherapeuticopportunitiesinliverdiseases |