Cyclic GMP-AMP synthase (cGAS) senses foreign DNA to produce 2'3'-cyclic GMP-AMP (2'3'-cGAMP). 2'3'-cGAMP is a second messenger that binds and activates the adaptor protein STING, which triggers the innate immune response. As a STING agonist, the small molecule 2'3'-cGAMP plays pivotal roles in antiviral defense and has adjuvant applications, and anti-tumor effects. 2'3'-cGAMP and its analogs are thus putative targets for immunotherapy and are currently being testedin clinical trials to treat solid tumors. However, several barriers to further development have emerged from these studies, such as evidence of immune and inflammatory side-effects, poor pharmacokinetics, and undesirable biodistribution. Here, we review the status of 2'3'-cGAMP research and outline the role of 2'3'-cGAMP in immune signaling, adjuvant applications, and cancer immunotherapy, as well as various 2'3'-cGAMP detection methods.

中文翻译：

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第二信使 2'3'-环状 GMP-AMP (2'3'-cGAMP)：合成、传输和降解。

环状 GMP-AMP 合酶 (cGAS) 感应外源 DNA 以产生 2'3'-环状 GMP-AMP (2'3'-cGAMP)。2'3'-cGAMP 是第二信使，可结合并激活衔接蛋白 STING，从而触发先天免疫反应。作为 STING 激动剂，小分子 2'3'-cGAMP 在抗病毒防御中起关键作用，并具有辅助应用和抗肿瘤作用。因此，2'3'-cGAMP 及其类似物是免疫治疗的推定靶标，目前正在临床试验中进行测试以治疗实体瘤。然而，这些研究出现了一些阻碍进一步发展的障碍，例如免疫和炎症副作用的证据、药代动力学差和不良的生物分布。在这里，我们回顾了 2'3'-cGAMP 研究的现状并概述了 2'3' 的作用