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.

中文翻译：

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STING 通路的激动剂和抑制剂：免疫治疗的潜在药物。

自 2008 年被发现以来，STING（干扰素基因刺激因子）通路逐渐被认为是免疫治疗的核心和有希望的靶点。STING 通路可以被环状二核苷酸 (CDN) 刺激，从而产生 I 型干扰素 (IFN)，用于癌症或其他疾病的免疫治疗。然而，CDNs的负电荷、亲水性和不稳定性阻碍了它们的进一步应用。此外，已发现 STING 通路的慢性激活与自身免疫性疾病有关，因为 IFN 过量产生。因此，STING 激动剂和抑制剂的研究和开发一直是治疗多种疾病的热点。过去几年，尤其是 2018 年，该领域的发展越来越快。在这里，这篇综述总结了 CDN 的合成和修改，详细介绍了非核苷酸激动剂的鉴定、递送系统和医学应用（例如个性化疫苗佐剂）的最新进展。此外，在这篇综述中，我们从共价和非共价抑制剂两个方面总结了 STING 抑制剂的进展。