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STING,小分子免疫调节剂的有前途靶点:综述。

STING, a promising target for small molecular immune modulator: A review.

机构信息

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

出版信息

Eur J Med Chem. 2021 Feb 5;211:113113. doi: 10.1016/j.ejmech.2020.113113. Epub 2020 Dec 18.

Abstract

Stimulator of interferon genes (STING) plays a crucial role in human innate immune system, which is gradually concerned following the emerging immunotherapy. Activated STING induces the production of type I interferons (IFNs) and proinflammatory cytokines through STING-TBK1-IRF3/NF-κB pathway, which could be applied into the treatment of infection, inflammation, and tumorigenesis. Here, we provided a detailed summary of STING from its structure, function and regulation. Especially, we illustrated the canonical or noncanonical cyclic dinucleotides (CDNs) and synthetic small molecules for STING activation or inhibition and their efficacy in related diseases. Importantly, we particularly emphasized the discovery, development and modification of STING agonist or antagonist, attempting to enlighten reader's mind for enriching small molecular modulator of STING. In addition, we summarized biological evaluation methods for the assessment of small molecules activity.

摘要

干扰素基因刺激物 (STING) 在人类先天免疫系统中发挥着至关重要的作用,随着新兴免疫疗法的出现,它逐渐受到关注。激活的 STING 通过 STING-TBK1-IRF3/NF-κB 途径诱导 I 型干扰素 (IFNs) 和促炎细胞因子的产生,可应用于感染、炎症和肿瘤发生的治疗。在这里,我们从 STING 的结构、功能和调节方面提供了详细的总结。特别是,我们阐述了用于 STING 激活或抑制的典型或非典型环二核苷酸 (CDNs) 和合成小分子及其在相关疾病中的疗效。重要的是,我们特别强调了 STING 激动剂或拮抗剂的发现、开发和修饰,试图为丰富 STING 的小分子调节剂启发读者的思路。此外,我们还总结了用于评估小分子活性的生物评价方法。

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