Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis

Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis

Blog Article

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, we identified dozens of compounds that inhibited TNF-induced Long Sleeve Shirts necroptosis.According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups.We then identified Ibrutinib as an inhibitor of RIPK3 Print-Scan-Present 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.