Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway

doi:10.1016/j.apsb.2020.03.001

	Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway
	Ding, Chunyong 1,2,3; Song, Zilan 2,3; Shen, Ancheng 2,3; Chen, Tingting 2,3; Zhang, Ao 1,2,3
刊名	ACTA PHARMACEUTICA SINICA B
	2020-12-01
卷号	10 期号:12 页码:2272-2298
关键词	Immunotherapy Anti-tumor cGAS STING TBK1 Small molecule modulators
ISSN号	2211-3835
DOI	10.1016/j.apsb.2020.03.001
通讯作者	Zhang, Ao(aozhang@simm.ac.cn)
英文摘要	Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors (ICIs) have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity. Particularly, the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S. Food and Drug Administration (FDA)-approved anti-programmed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies. However, the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity. Indeed, the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes-TANK-binding kinase 1 (cGAS-STING-TBK1) axis is now appreciated as the major signaling pathway in innate immune response across different species. Aberrant signaling of this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection and cancers. In this perspective, we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS-STING-TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy. Meanwhile, highlights on the clinical candidates, limitations and challenges, as well as future directions in this field are also discussed. Further, small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
资助项目	Natural Science Foundation of China (China)[81773565] ; Natural Science Foundation of China (China)[21877120] ; Natural Science Foundation of China (China)[81703327] ; Natural Science Foundation of China (China)[81430080] ; Natural Science Foundation of China (China)[81573452] ; Natural Science Foundation of China (China)[81773767] ; Key Program of the Frontier Science of the Chinese Academy of Sciences (China)[160621] ; Strategic Priority Research Program of the Chinese Academy of Sciences (China)[XDA12020374] ; Shanghai Jiao Tong University (China)
WOS关键词	CYCLIC GMP-AMP ; CANCER-IMMUNOTHERAPY ; STING PATHWAY ; CRYSTAL-STRUCTURE ; NEXT-GENERATION ; DNA ; TBK1 ; ACTIVATION ; INHIBITORS ; DISCOVERY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号	WOS:000599622800002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296282]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Ao
作者单位	1.Shanghai Jiao Tong Univ, Sch Pharm, Res Lab Med Chem Biol & Frontiers Drug Discovery, Shanghai 200240, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Ding, Chunyong,Song, Zilan,Shen, Ancheng,et al. Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway[J]. ACTA PHARMACEUTICA SINICA B,2020,10(12):2272-2298.
APA	Ding, Chunyong,Song, Zilan,Shen, Ancheng,Chen, Tingting,&Zhang, Ao.(2020).Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway.ACTA PHARMACEUTICA SINICA B,10(12),2272-2298.
MLA	Ding, Chunyong,et al."Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway".ACTA PHARMACEUTICA SINICA B 10.12(2020):2272-2298.