TitleDiscovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein
AuthorsYan, Bo
Liu, Lei
Huang, Shaoqiang
Ren, Yan
Wang, Huayi
Yao, Zhenglin
Li, Lin
Chen, She
Wang, Xiaodong
Zhang, Zhiyuan
AffiliationPeking Univ, Sch Life Sci, Beijing 100871, Peoples R China.
Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China.
Chinese Acad Med Sci, Beijing 100730, Peoples R China.
Natl Inst Biol Sci, Beijing 102206, Peoples R China.
Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China.
Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China.
Wang, XD (reprint author), Chinese Acad Med Sci, Beijing 100730, Peoples R China.
Wang, XD
Zhang, ZY (reprint author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
Zhang, ZY (reprint author), Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China.
KeywordsCELL-DEATH
MLKL
NECROSIS
RIP3
INFLAMMATION
ACTIVATION
Issue Date2017
PublisherCHEMICAL COMMUNICATIONS
CitationCHEMICAL COMMUNICATIONS.2017,53(26),3637-3640.
AbstractWe 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.
URIhttp://hdl.handle.net/20.500.11897/474089
ISSN1359-7345
DOI10.1039/c7cc00667e
IndexedSCI(E)
Appears in Collections:生命科学学院

Files in This Work
There are no files associated with this item.

Web of Science®



Checked on Last Week

Scopus®



Checked on Current Time

百度学术™



Checked on Current Time

Google Scholar™





License: See PKU IR operational policies.