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 merlin wizard costume small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis.According to the mechanisms by which they inhibited necroptosis, these g35 coupe fender 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.