更新于：2024-11-01

TRIM29 x STING

更新于：2024-11-01

基本信息

关联

项与 TRIM29 x STING 相关的药物

SB-24011

靶点

STING x TRIM29

作用机制

STING1抑制剂 [+1]

在研机构

Sparkbiopharma Co., Ltd.

原研机构

Sparkbiopharma Co., Ltd.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TRIM29 x STING 相关的临床结果

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100 项与 TRIM29 x STING 相关的转化医学

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0 项与 TRIM29 x STING 相关的专利（医药）

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项与 TRIM29 x STING 相关的文献（医药）

2023-04-24·Angewandte Chemie International Edition

Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy

Article

作者: Park, Seung Bum ; Choi, Yoona ; Cho, Wansang ; Choi, Young Il ; Park, Jong Beom ; Kim, Caroline E ; Park, Jun-Gyu ; Kim, Ju Hee ; Lee, Dong-Sup ; Narayana, Chintam ; Won, Solchan ; Yim, Junhyeong ; Yi, Sihyeong

AbstractModulating target proteins via the ubiquitin‐proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein‐protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING‐TRIM29 E3 ligase interaction, thus blocking TRIM29‐induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti‐PD‐1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno‐oncology.

2023-01-01·Cell Death & Differentiation

UFL1 promotes antiviral immune response by maintaining STING stability independent of UFMylation

Article

作者: Liu, Yang ; Xu, Sheng ; Han, Dan ; Huang, Jingyi ; Chen, Yining ; Tao, Yijie ; Zou, Zui ; Yin, Shulei ; Yu, Yizhi ; Li, Chunzhen

AbstractThe precise regulation of STING homeostasis is essential for its antiviral function. Post-translational modification, especially ubiquitination, is important for the regulation of STING homeostasis. Previous studies have focused on how STING is degraded, but little is known about its maintenance. Here, we show that UFM1 specific ligase UFL1 promotes innate immune response by maintaining STING expression independent of UFMylation. Mechanistically, UFL1 inhibits TRIM29 to interact with STING, thereby reducing its ubiquitination at K338/K347/K370 and subsequent proteasomal degradation. DNA virus infection reduces the UFL1 expression, which may promote STING degradation and facilitate viral expansion. Our study identifies UFL1 as a crucial regulator for the maintenance of STING stability and antiviral function, and provides novel insights into the mechanistic explanation for the immunological escape of DNA virus.

2022-05-01·Pancreas

Reduced Tripartite Motif-Containing Protein 29 Deteriorates the Severity of Severe Acute Pancreatitis

Article

作者: Wang, Leilei ; Ji, Suzhen

ObjectivesSevere acute pancreatitis (SAP) is the most serious subtype of acute pancreatitis, manifested as multiple-organ failure resulting in high morbidity and mortality. Based on the role of tripartite motif-containing protein 29 (TRIM29) in immune responses, we aimed to explore its effect on SAP.MethodsPeripheral blood monocyte cells from the SAP or non-SAP patients, as well as bone marrow–derived macrophages from wild-type, TRIM29−/−, or stimulator of interferon genes (STING)−/− mice after injecting 50 mg/kg of cerulein to induce SAP, were isolated to analyze the role of TRIM29 and STING in the SAP.ResultsTripartite motif-containing protein 29 was significantly reduced in SAP patients. Compared with wild-type mice, TRIM29 deficiency mice displayed more severe symptom of acute pancreatitis after cerulein injection, which were lost in TRIM29−/−STING−/− mice. Moreover, interferon and its related genes, as well as STING degradation, were decreased in TRIM29−/− mice.ConclusionsOur study demonstrated that TRIM29 negatively regulated the severity of SAP by degrading STING at its downstream, suggesting that TRIM29 and STING might serve as therapeutic targets for SAP.