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Methods Mol Biol. 2018;1857:19-33. doi: 10.1007/978-1-4939-8754-2_3.

Chemical Library Screens to Identify Pharmacological Modulators of Necroptosis.

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Medical Scientist Training Program, Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA.


Necroptosis is mediated by the formation of the detergent-insoluble necrosome complex between Ser/Thr kinases RIPK1 and RIPK3, which mediates RIPK3-dependent phosphorylation and activation of the critical necroptosis effector MLKL. Small molecule screens have been instrumental in the development of new chemical probes for this pathway. In this chapter, we describe several cellular assays that are readily amendable for the identification of new modulators of necroptosis as well as secondary assays to facilitate initial characterization of the mode of activity of small molecule hits.


Apoptosis; Complex 2b; MLKL; Necroptosis; Necrosome; RIPK1; RIPK3

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