High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway

doi:10.1016/j.apsb.2018.07.005

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	High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway
	Yuliantie, Elita 2,3,5; Dai, Xinchuan 3,5; Yang, Dehua2,3,5 ; Crack, Peter J.1; Wang, Ming-Wei2,3,4,5
刊名	ACTA PHARMACEUTICA SINICA B
	2018-10
卷号	8 期号:6 页码:889-899
关键词	High-throughput screening Interferon alpha receptor Secreted embryonic alka-line phosphatase JAK-STAT IFN regulatory factor Inhibitor
ISSN号	2211-3835
DOI	10.1016/j.apsb.2018.07.005
文献子类	Article
英文摘要	Interferons (IFNs) are cytokines with fundamental roles in resistance to infections, cancer and other diseases. Type-I IFNs, interferon alpha (IFN-alpha) and interferon beta (IFN-beta), act through a shared receptor complex (IFNAR) comprised of IFNAR1 and IFNAR2 subunits. Binding of type-I IFN to IFNAR1 will robustly activate Janus activated kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Aberrant activation of the type-I IFN response results in a spectrum of disorders called interferonopathies. The purpose of this research is to develop an assay for high-throughput screening (HTS) of small molecule inhibitors of the type-I IFN signaling pathway. Inhibition of type-I IFN signaling can be beneficial in terms of therapeutic use and understanding the underlying mechanism of action. We report here a HTS campaign with the secreted embryonic alkaline phosphatase (SEAP) reporter gene assay against 32,000 compounds which yielded 25 confirmed hits. These compounds were subsequently characterized for their cytotoxicity, effects on STAT phosphorylation and activities in IFN regulatory factor (IRF) transcription.
资助项目	Shanghai Science and Technology Development Fund[MWW: 15DZ2291600] ; Thousand Talents Program in China[MWW: [2011] ; Australian Research Council Future Fellowship[00000000] ; CAS President's International Fellowship Initiative (PIFI)[00000000]
WOS关键词	ACTIVATION ; IDENTIFICATION ; TRANSDUCER ; ASSAYS ; CELLS
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:000451117700005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279545]
专题	国家新药筛选中心
通讯作者	Wang, Ming-Wei
作者单位	1.Univ Melbourne, Dept Pharmacol & Therapeut, Parkville, Vic 3010, Australia; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 4.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Yuliantie, Elita,Dai, Xinchuan,Yang, Dehua,et al. High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway[J]. ACTA PHARMACEUTICA SINICA B,2018,8(6):889-899.
APA	Yuliantie, Elita,Dai, Xinchuan,Yang, Dehua,Crack, Peter J.,&Wang, Ming-Wei.(2018).High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway.ACTA PHARMACEUTICA SINICA B,8(6),889-899.
MLA	Yuliantie, Elita,et al."High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway".ACTA PHARMACEUTICA SINICA B 8.6(2018):889-899.