Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy
Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy
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STING 通路的激动剂和抑制剂：免疫治疗的潜在药物
DOI：
10.1002/med.21649
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发表时间：
2019-12
影响因子：
13.3
通讯作者：
Li Yan-Mei
中科院分区：
文献类型：
--
作者：
Wu Jun-Jun;Zhao Lang;Hu Hong-Guo;Li Wen-Hao;Li Yan-Mei
自2008年被发现以来，STING（干扰素基因刺激因子）途径逐渐被认为是免疫治疗的核心和有希望的靶点。环状二核苷酸（cdn）可以刺激STING通路，导致I型干扰素（IFN）的产生，用于癌症或其他疾病的免疫治疗。然而，cdn的负电荷、亲水性和不稳定性阻碍了其进一步的应用。此外，STING途径的慢性激活已被发现与自身免疫性疾病有关，如IFN过量产生。因此，研究和开发STING激动剂和抑制剂已成为治疗多种疾病的热门领域。过去几年，特别是2018年，这一领域的进展越来越快。本文综述了cdn的合成和修饰、非核苷酸激动剂的鉴定、cdn在递送系统和医学应用方面的最新进展，如个性化疫苗佐剂。此外，本文从共价抑制剂和非共价抑制剂两个方面综述了STING抑制剂的研究进展。
Since being discovered in 2008, the STING (stimulator of interferon genes) pathway has gradually been recognized as a central and promising target for immunotherapy. The STING pathway can be stimulated by cyclic dinucleotides (CDNs), leading to the type I interferons (IFN) production for immunotherapy for cancer or other diseases. However, the negative charges, hydrophilicity, and instability of CDNs have hindered their further applications. In addition, chronic activation of the STING pathway has been found to be involved in autoimmune diseases as IFN overproduction. Thus, research and development of STING agonists and inhibitors has been a hot field for the treatment of several diseases. The past several years, especially 2018, has seen increasingly rapid advances in this field. Here, this review summarizes the synthesis and modification of CDNs, the identification of nonnucleotide agonists, the recent progress in delivery systems and the medical applications, such as personalized vaccine adjuvants, in detail. In addition, in this review, we summarize the STING inhibitors’ advances from two aspects, covalent, and noncovalent inhibitors.
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DOI：
10.1073/pnas.1512832112
发表时间：
2015-12-15
影响因子：
11.1
作者：
Demaria, Olivier;De Gassart, Aude;Gilliet, Michel
通讯作者：
Gilliet, Michel
DOI：
10.1073/pnas.1806239115
发表时间：
2018-08-14
影响因子：
11.1
作者：
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通讯作者：
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DOI：
10.1056/nejmoa1312625
发表时间：
2014-08-07
期刊：
The New England journal of medicine
影响因子：
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作者：
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通讯作者：
Goldbach-Mansky R
影响因子：
8.8
作者：
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通讯作者：
Gajewski TF
影响因子：
2.9
作者：
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通讯作者：
Mittelbronn M