Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis
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 inh...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05353-5 |
| _version_ | 1797557116986195968 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fangmin Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:12:37Z |
| format | Article |
| id | doaj.art-01e87df1633b49d091cb0154e63369ba |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:12:37Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-01e87df1633b49d091cb0154e63369ba2023-11-20T10:35:36ZengNature PortfolioCommunications Biology2399-36422023-09-016111210.1038/s42003-023-05353-5Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosisFangmin Huang0Jiankun Liang1Yingying Lin2Yushi Chen3Fen Hu4Jianting Feng5Qiang Zeng6Zeteng Han7Qiaofa Lin8Yan Li9Jingyi Li10Lanqin Wu11Lisheng Li12The School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityThe School of Basic Medical Sciences, Fujian Medical UniversityAbstract 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.https://doi.org/10.1038/s42003-023-05353-5 |
| spellingShingle | 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 Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis Communications Biology |
| title | Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis |
| title_full | Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis |
| title_fullStr | Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis |
| title_full_unstemmed | Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis |
| title_short | Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis |
| title_sort | repurposing of ibrutinib and quizartinib as potent inhibitors of necroptosis |
| url | https://doi.org/10.1038/s42003-023-05353-5 |
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