Small molecules targeting the innate immune cGAS‒STING‒TBK1 signaling pathway.

Autor:	Ding C; 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., Song Z; 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., Shen A; 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., Chen T; 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., Zhang A; 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.
Jazyk:	angličtina
Zdroj:	Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2020 Dec; Vol. 10 (12), pp. 2272-2298. Date of Electronic Publication: 2020 Mar 13.
DOI:	10.1016/j.apsb.2020.03.001
Abstrakt:	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. Competing Interests: Authors declare absence of conflict of interest. (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu