Repurposing anticancer drugs for targeting necroptosis

Cell Cycle
Simone Fulda

Abstract

Necroptosis represents a form of programmed cell death that can be engaged by various upstream signals, for example by ligation of death receptors, by viral sensors or by pattern recognition receptors. It depends on several key signaling proteins, including the kinases Receptor-Interacting Protein (RIP)1 and RIP3 and the pseudokinase mixed-lineage kinase domain-like protein (MLKL). Necroptosis has been implicated in a number of physiological and pathophysiological conditions and is disturbed in many human diseases. Thus, targeted interference with necroptosis signaling may offer new opportunities for the treatment of human diseases. Besides structure-based drug design, in recent years drug repositioning has emerged as a promising alternative to develop drug-like compounds. There is accumulating evidence showing that multi-targeting kinase inhibitors, for example Dabrafenib, Vemurafenib, Sorafenib, Pazopanib and Ponatinib, used for the treatment of cancer also display anti-necroptotic activity. This review summarizes recent evidence indicating that some anticancer kinase inhibitors also negatively affect necroptosis signaling. This implies that some cancer therapeutics may be repurposed for other pathologies, e.g. ischemic or in...Continue Reading

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Citations

Jun 4, 2020·The Journal of Infectious Diseases·Sarah M BenoCarlos J Orihuela
Feb 20, 2021·Cell Death & Disease·Martina RaudenskáMichal Masařík
Jun 3, 2021·Cancers·Radka MichalkovaJan Mojzis
Nov 12, 2021·Aging Cell·Sabira MohammedSathyaseelan S Deepa
Nov 30, 2021·Basic & Clinical Pharmacology & Toxicology·Qi ZhaoLijun Yang

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Methods Mentioned

BETA
pull-down
affinity purifications

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