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Communications Biology

Communications Biology

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Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis.

Published:23 September 2023 DOI: 10.1038/s42003-023-05353-5 PMID: 37741898
Fangmin Huang, Jiankun Liang, Yingying Lin, Yushi Chen, Fen Hu, Jianting Feng, Qiang Zeng, Zeteng Han, Qiaofa Lin, Yan Li, Jingyi Li, Lanqin Wu, Lisheng Li

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 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.

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Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Ibrutinib 936563-96-1 C25H24N6O2 741 suppliers $5.00-$1360.00
Ibrutinib 936563-96-1 C25H24N6O2 741 suppliers $5.00-$1360.00
Propidium iodide 25535-16-4 C27H34IN4+ 471 suppliers $12.00-$7450.00
Propidium iodide 25535-16-4 C27H34IN4+ 471 suppliers $12.00-$7450.00
Necrostatin-1 4311-88-0 C13H13N3OS 262 suppliers $12.00-$3635.00
Necrostatin-1 4311-88-0 C13H13N3OS 262 suppliers $12.00-$3635.00
Quizartinib 950769-58-1 C29H32N6O4S 235 suppliers $13.00-$5280.00
Quizartinib 950769-58-1 C29H32N6O4S 235 suppliers $13.00-$5280.00
Gilteritinib 1254053-43-4 C29H44N8O3 204 suppliers $12.00-$1815.00
Gilteritinib 1254053-43-4 C29H44N8O3 204 suppliers $12.00-$1815.00

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