Targeting MyD88: Therapeutic mechanisms and potential applications of the specific inhibitor ST2825,Inflammation Research

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Targeting MyD88: Therapeutic mechanisms and potential applications of the specific inhibitor ST2825
Inflammation Research ( IF 4.8 ) Pub Date : 2023-10-09 , DOI: 10.1007/s00011-023-01801-4
Meiqi Liu ₁ , Wenyan Kang ₁ , Zhizhong Hu ₁ , Chengkun Wang ₁ , Yang Zhang ₁

Affiliation

Background

Myeloid differentiation factor-88 (MyD88) is a crucial adapter protein that coordinates the innate immune response and establishes an adaptive immune response. The interaction of the Toll/Interleukin-1 receptor (IL-1R) superfamily with MyD88 triggers the activation of various signalling pathways such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), promoting the production of a variety of immune and inflammatory mediators and potentially driving the development of a variety of diseases.

Objective

This article will explore the therapeutic potential and mechanism of the MyD88-specific inhibitor ST2825 and describe its use in the treatment of several diseases. We envision future research and clinical applications of ST2825 to provide new ideas for the development of anti-inflammatory drugs and disease-specific drugs to open new horizons for the prevention and treatment of related inflammatory diseases.

Materials and methods

This review analysed relevant literature in PubMed and other databases. All relevant studies on MyD88 inhibitors and ST2825 that were published in the last 20 years were used as screening criteria. These studies looked at the development and improvement of MyD88 inhibitors and ST2825.

Results

Recent evidence using the small-molecule inhibitor of ST2825 has suggested that blocking MyD88 activity can be used to treat diseases such as neuroinflammation, inflammatory diseases such as acute liver/kidney injury, or autoimmune diseases such as systemic lupus erythematosus and can affect transplantation immunity. In addition, ST2825 has potential therapeutic value in B-cell lymphoma with the MyD88 L265P mutation.

Conclusion

Targeting MyD88 is a novel therapeutic strategy, and scientific research is presently focused on the development of MyD88 inhibitors. The peptidomimetic compound ST2825 is a widely studied small-molecule inhibitor of MyD88. Thus, ST2825 may be a potential therapeutic small-molecule agent for modulating host immune regulation in inflammatory diseases and inflammatory therapy.

中文翻译：

靶向MyD88：特异性抑制剂ST2825的治疗机制和潜在应用

背景

骨髓分化因子 88 (MyD88) 是一种重要的衔接蛋白，可协调先天免疫反应并建立适应性免疫反应。Toll/白细胞介素-1受体（IL-1R）超家族与MyD88的相互作用触发多种信号通路的激活，例如核因子-κB（NF-κB）和激活蛋白-1（AP-1），促进生产多种免疫和炎症介质，并可能驱动多种疾病的发展。