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

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

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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 immu-nogenicity.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 mole-cule modulators targeting the cGAS-STING-TBKl 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 inhib-itors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.

ImmunotherapyAnti-tumorcGASSTINGTBK1Small molecule modulators

Chunyong Ding、Zilan Song、Ancheng Shen、Tingting Chen、Ao Zhang

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Research Laboratory of Medicinal Chemical Biology & Frontiers on Drug Discovery (RLMCBFDD),School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China

CAS Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica (SIMM),Chinese Academy of Sciences,Shanghai 201203,China

University of Chinese Academy of Sciences,Beijing 100049,China

grants from Natural Science Foun-dation of Chinagrants from Natural Science Foun-dation of Chinagrants from Natural Science Foun-dation of Chinagrants from Natural Science Foun-dation of Chinagrants from Natural Science Foun-dation of Chinagrants from Natural Science Foun-dation of Chinagrants from Natural Science Foun-dation of Chinagrants from Natural Science Foun-dation of ChinaSupporting grants from the Key Program of the Frontier Science of the Chinese Academy of SciencesSupporting grants from the Key Program of the Frontier Science of the Chinese Academy of SciencesStrategic Priority Research Program of the Chinese Academy of SciencesStrategic Priority Research Program of the Chinese Academy of Sciences

Nos.817735652187712081703327814300808157345281773767China160621ChinaXDA12020374China

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(12)
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