Discovery of a new class of highly potent necroptosis inhibitors   targeting the mixed lineage kinase domain-like protein

doi:10.1039/c7cc00667e

CORC > 北京大学 > 生命科学学院

	Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein
	Yan, Bo ; Liu, Lei ; Huang, Shaoqiang ; Ren, Yan ; Wang, Huayi ; Yao, Zhenglin ; Li, Lin ; Chen, She ; Wang, Xiaodong ; Zhang, Zhiyuan
刊名	CHEMICAL COMMUNICATIONS
	2017
关键词	CELL-DEATH MLKL NECROSIS RIP3 INFLAMMATION ACTIVATION
DOI	10.1039/c7cc00667e
英文摘要	We report the development of novel Mixed Lineage Kinase Domain-Like protein (MLKL) inhibitors with single nanomolar potency (compound 15 is also named as TC13172). Using the converting biochemistry to chemistry activity-based protein profiling (BTC-ABPP) method, we were able to determine that the inhibitors covalently bind to Cysteine86 (Cys-86) of MLKL. This is the first example of the use of LC-MS/MS to identify the binding site of an MLKL inhibitor. The novel MLKL inhibitors provide powerful tools to study the biological function of MLKL and demonstrate that MLKL should be viewed as a druggable target.; National Major Scientific and Technological Special Project for "Significant New Drugs Development'' during the Twelfth Five-year Plan from the Chinese Ministry of Science and Technology [2013ZX0950910]; SCI(E); ARTICLE; 26; 3637-3640; 53
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/474089]
专题	生命科学学院
推荐引用方式 GB/T 7714	Yan, Bo,Liu, Lei,Huang, Shaoqiang,et al. Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein[J]. CHEMICAL COMMUNICATIONS,2017.
APA	Yan, Bo.,Liu, Lei.,Huang, Shaoqiang.,Ren, Yan.,Wang, Huayi.,...&Zhang, Zhiyuan.(2017).Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein.CHEMICAL COMMUNICATIONS.
MLA	Yan, Bo,et al."Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein".CHEMICAL COMMUNICATIONS (2017).