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环状GMP-AMP合酶(cGAS)抑制剂作为自身免疫性和炎性疾病的潜在治疗方法

Inhibitors of the Cyclic GMP-AMP Synthase (cGAS) as Potential Treatment for Autoimmune and Inflammatory Diseases.

作者信息

Abdel-Magid Ahmed F

机构信息

PI Health Sciences, 100 Jade Park, Chelsea, Alabama 35043, United States.

出版信息

ACS Med Chem Lett. 2024 Aug 22;15(9):1424-1426. doi: 10.1021/acsmedchemlett.4c00392. eCollection 2024 Sep 12.

DOI:10.1021/acsmedchemlett.4c00392
PMID:39291025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11403758/
Abstract

The invention in this patent application relates to macrocyclic benzimidazole derivatives represented herein generally by Formula 1. The compounds of Formula 1 are cGAS inhibitors and may potentially provide treatments of autoimmune diseases such as systemic lupus erythematosus, systemic sclerosis (SSc), interferonopathies, and others.

摘要

本专利申请中的发明涉及一般由式1表示的大环苯并咪唑衍生物。式1的化合物是环鸟苷酸合成酶(cGAS)抑制剂,可能为自身免疫性疾病如系统性红斑狼疮、系统性硬化症(SSc)、干扰素病等提供治疗方法。

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本文引用的文献

1
Agonists and Inhibitors of the cGAS-STING Pathway.cGAS-STING 通路的激动剂和抑制剂。
Molecules. 2024 Jun 30;29(13):3121. doi: 10.3390/molecules29133121.
2
The multiple faces of cGAS-STING in antitumor immunity: prospects and challenges.cGAS-STING在抗肿瘤免疫中的多面性:前景与挑战
Med Rev (2021). 2024 Apr 15;4(3):173-191. doi: 10.1515/mr-2023-0061. eCollection 2024 Jun.
3
The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS.cGAS 催化 2'-5'/3'-5'-cGAMP 合成的结构基础。
Nat Commun. 2024 May 13;15(1):4012. doi: 10.1038/s41467-024-48365-3.
4
cGAS-STING, an important signaling pathway in diseases and their therapy.环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白(cGAS-STING),是疾病及其治疗中的一条重要信号通路。
MedComm (2020). 2024 Mar 23;5(4):e511. doi: 10.1002/mco2.511. eCollection 2024 Apr.
5
Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing.细胞质 DNA 感应的 cGAS-STING 途径的调控和功能。
Nat Immunol. 2016 Sep 20;17(10):1142-9. doi: 10.1038/ni.3558.
6
Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.环鸟苷酸-腺苷酸合酶是一种胞质 DNA 传感器,可激活 I 型干扰素途径。
Science. 2013 Feb 15;339(6121):786-91. doi: 10.1126/science.1232458. Epub 2012 Dec 20.