Curadev Pharma Pvt. Ltd., Noida, Uttar Pradesh, India.
Curadev Pharma Ltd., Sandwich, Kent, United Kingdom.
PLoS One. 2020 Sep 10;15(9):e0237743. doi: 10.1371/journal.pone.0237743. eCollection 2020.
The cGAS/STING pathway initiates an innate immune response when DNA is detected in the cytosol. DNA bound cGAS synthesizes cyclic dinucleotides which bind and activate the adaptor STING, leading to downstream secretion of Type I interferons and other pro-inflammatory NFκB pathway cytokines. In the mouse, the STING driven innate immune response is central to immune based clearance of various tumors and this has triggered a significant effort focused on the discovery of human STING agonists for the treatment of cancer. This report uses an in vitro kinase assay to show that G10, a previously identified STING pathway activator is actually a weak but direct STING agonist and identifies other more potent leads.
当细胞质中检测到 DNA 时，cGAS/STING 途径会引发先天免疫反应。与 DNA 结合的 cGAS 合成环二核苷酸，该环二核苷酸结合并激活衔接蛋白 STING，导致 I 型干扰素和其他促炎 NFκB 途径细胞因子的下游分泌。在小鼠中，由 STING 驱动的先天免疫反应是基于免疫清除各种肿瘤的核心，这引发了一项旨在发现用于治疗癌症的人类 STING 激动剂的重大努力。本报告使用体外激酶测定表明，先前鉴定的 STING 途径激活剂 G10 实际上是一种弱但直接的 STING 激动剂，并确定了其他更有效的先导化合物。
