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Stopping unwanted cell death: Implications for drug discovery
Date:4/13/2008

BOSTON (April 13, 2008, 1:00 p.m. ET) Research published in Nature Chemical Biology reveals that three specific inhibitors of a cell death pathway, termed necroptosis, all target and inhibit RIP1 kinase, a protein that can direct cells into necrosis. Induced by trauma such as a heart attack or stroke, this form of necrotic death can result in tissue damage contributing to death or long-term disability. The findings present a novel avenue for drug development.

Our research found that RIP1 kinase can be inhibited by three small molecules: necrostatin-1, -3 and -5, reports first author Alexei Degterev, PhD, assistant professor at Tufts University School of Medicine and member of the biochemistry program faculty of the Sackler School of Graduate Biomedical Sciences. Overall, these data establish RIP1 kinase as a new target for therapeutic drug development for human diseases involving necrotic tissue injury, and they establish necrostatins as first-in-class potent and selective inhibitors of RIP1 kinase, the authors write, including last author, Junying Yuan, PhD, professor at Harvard Medical School.

Necrosis is relevant to many diseases, particularly those that involve an acute event, such as heart attack or stroke. Cells are programmed to die when they reach the end of their lifecycle and that regulated process is called apoptosis. Cells can also be killed through pathways not controlled by apoptosis. Until recently, this type of cell death, termed necrosis, was believed to be unregulated, a type of accidental cell death caused when cells are placed under extreme stress such as during a heart attack, stroke or organ failure, says Degterev.

Previous research, as well as research by others, determined that necroptosis, one type of necrosis, is regulated (like apoptosis) and has a specific biochemical pathway. Through our previous work, we have developed potent and specific small molecules capable of preventing necroptosis in isola
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Contact: Siobhan E. Gallagher
siobhan.gallagher@tufts.edu
617-636-6586
Tufts University, Health Sciences
Source:Eurekalert  

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