tosylphenylalanyl-chloromethyl-ketone and Chemical-and-Drug-Induced-Liver-Injury

Necrosis is the main mode of cell death, which leads to multiple clinical conditions affecting hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering therapeutics development. Here, we identify key proteolytic activities essential for necrosis using various biochemical approaches, enzymatic assays, medicinal chemistry, and siRNA library screening. These findings provide strategies to treat and prevent necrosis, including known medicines used for other indications, siRNAs, and establish a platform for the design of new inhibitory molecules. Indeed, inhibitors of these pathways demonstrated protective activity

Topics: Animals; Brain Injuries, Traumatic; Cell Death; Chemical and Drug Induced Liver Injury; High-Throughput Screening Assays; Humans; Mice, Inbred BALB C; Mice, Inbred C57BL; Myocardial Infarction; Necroptosis; Necrosis; Pancreatic Elastase; Protease Inhibitors; RNA, Small Interfering; U937 Cells