用小分子阻断环状二核苷酸-cGAS-STING轴。
Interrupting cyclic dinucleotide-cGAS-STING axis with small molecules.
作者信息
Sintim Herman O, Mikek Clinton G, Wang Modi, Sooreshjani Moloud A
机构信息
Department of Chemistry , Purdue University , 560 Oval Drive , West Lafayette , IN 47907 , USA . Email:
Institute for Drug Discovery , Purdue University , 720 Clinic Drive , West Lafayette , IN 47907 , USA.
出版信息
Medchemcomm. 2019 Aug 15;10(12):1999-2023. doi: 10.1039/c8md00555a. eCollection 2019 Dec 1.
The cyclic dinucleotide-cGAS-STING axis plays important roles in host immunity. Activation of this signaling pathway, cytosolic sensing of bacterial-derived c-di-GMP/c-di-AMP or host-derived cGAMP, leads to the production of inflammatory interferons and cytokines that help resolve infection. Small molecule activators of the cGAS-STING axis have the potential to augment immune response against various pathogens or cancer. The aberrant activation of this pathway, due to gain-of-function mutations in any of the proteins that are part of the signaling axis, could lead to various autoimmune diseases. Inhibiting various nodes of the cGAS-STING axis could provide relief to patients with autoimmune diseases. Many excellent reviews on the cGAS-STING axis have been published recently, and these have mainly focused on the molecular details of the cGAS-STING pathway. This review however focuses on small molecules that can be used to modulate various aspects of the cGAS-STING pathway, as well as other parallel inflammatory pathways.
环状二核苷酸 - cGAS - STING轴在宿主免疫中发挥重要作用。该信号通路的激活，即对细菌来源的c - di - GMP/c - di - AMP或宿主来源的cGAMP的胞质感知，会导致炎症性干扰素和细胞因子的产生，有助于消除感染。cGAS - STING轴的小分子激活剂有增强针对各种病原体或癌症的免疫反应的潜力。由于该信号轴中任何一种蛋白质的功能获得性突变，导致该通路的异常激活，可能会引发各种自身免疫性疾病。抑制cGAS - STING轴的各个节点可为自身免疫性疾病患者提供缓解。最近已经发表了许多关于cGAS - STING轴的优秀综述，这些综述主要集中在cGAS - STING通路的分子细节上。然而，本综述关注的是可用于调节cGAS - STING通路以及其他平行炎症通路各个方面的小分子。
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