Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis

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 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 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. Screening a library of compounds identifies several inhibitors of TNF-induced necroptosis, including Ibrutinib as an inhibitor of RIPK3 and Quizartinib as an indirect RIPK1 kinase activity inhibitor.

Automated summary

A study discovered multiple compounds that inhibit TNF-induced necroptosis by screening a compound library. These compounds were classified into different groups based on their mechanisms of action. Further investigation identified Ibrutinib as an inhibitor of RIPK3 and Quizartinib as a protector against TNF-induced systemic inflammatory response syndrome by inhibiting the activation of RIPK1. The findings suggest new potential approaches for treating necroptosis-related diseases.