- Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein.
Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein.
Chemical communications (Cambridge, England) (2017-03-08)
Bo Yan, Lei Liu, Shaoqiang Huang, Yan Ren, Huayi Wang, Zhenglin Yao, Lin Li, She Chen, Xiaodong Wang, Zhiyuan Zhang
PMID28267172
ZUSAMMENFASSUNG
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.
MATERIALIEN