Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis

Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis

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Abstract Necroptosis is a form of regulated cell death that has been implicated in multiple diseases.TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL.In this study, by screening of a small-compound library, micarta iphone case we identified dozens of compounds that inhibited TNF-induced necroptosis.According to the mechanisms by which they 15-eg1053cl inhibited necroptosis, these compounds were classified into different groups.

We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1.Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases.