DataVXAdvanced SciencePaper
journal article·2025-06Open access

Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury

Xiao Zhuang, Shuang Shi, Shuo Liu, Yaqiong Jiao, Bin Huang, Yinghong Yang, Li Yang, Xinquan Yang, Hui Wang, Chunhui Liang, Dandan Song, Huaxiang Yu, Dan Zou, Qi Sun, Shu Yang, Chengqian Yin, Jian Li, Yiming Liu, Junxia Min, Fudi Wang, Yong Nian, Lutao Du, Bo Chu

Advanced Science· Volume 12· Issue 23
Publisher pageOpen full text
Source abstract

Abstract

Abstract Ferroptosis is a newly identified cell death triggered by iron‐induced lipid peroxidation. Numerous studies reveal that ferroptosis participates in multiple types of tissue injury including ischaemia–reperfusion (I/R) injury and doxorubicin (Dox)‐induced damage. Targeting ferroptosis is a promising approach for disease treatment as the blockade of ferroptosis efficiently alleviates the symptoms. However, no known ferroptosis inhibitors have been used for clinical treatment. Although certain clinical compounds act as ferroptosis inhibitors in vitro, whether these drugs cure tissue injury by suppressing ferroptosis is little known. Here, by screening a large panel of drugs used in the clinic, it is identified that dipyridamole significantly attenuates Dox or I/R‐induced cardiac injury. Moreover, dipyridamole can achieve a good therapeutic effect on liver and kidney injury. Mechanistically, dipyridamole‐mediated ferroptosis inhibition is strictly dependent on solute carrier family 7 member 11 (SLC7A11). Dipyridamole down‐regulates the expression of ring finger protein 126 (RNF126), which is an E3 ligase to ubiquitinate SLC7A11 for proteasome degradation. Deficiency of SLC7A11 largely blocks the protective role of dipyridamole in vitro and in vivo. Together, the findings uncover that dipyridamole acts as a clinical compound to alleviate organ injury via suppressing ferroptosis, providing novel insights into the clinical therapy for ferroptosis‐related tissue damage.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Ferroptosis and cancer prognosis · Cancer, Lipids, and Metabolism · RNA modifications and cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 China

Department of Clinical Laboratory The Second Hospital of Shandong University Jinan 250012 China

Department of Geriatric Medicine Qilu Hospital of Shandong University Jinan 250012 China

Department of General Practice Qilu Hospital of Shandong University Jinan 250012 China

Institute for Cancer Research Shenzhen Bay Laboratory Shenzhen 518107 China

Department of Respiratory and Critical Care Medicine Zhengzhou University People's Hospital Henan Provincial People's Hospital Zhengzhou 450003 China

The First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou 310058 China

Department of Emergency Medicine and Chest Pain Center Qilu Hospital of Shandong University Jinan 250012 China

Department of Biochemistry and Molecular Biology Shandong University School of Medicine Jinan 250012 China

College of Pharmacy Nanjing drum tower hospital Nanjing University of Chinese Medicine Nanjing 210023 China

Department of Neurology Qilu Hospital of Shandong University Jinan 250012 China

The First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine Hangzhou 310058 China

Department of Clinical Laboratory Qilu Hospital of Shandong University Jinan 250012 China

Shandong Provincial Key Laboratory of Innovation Technology in Laboratory Medicine Jinan 250012 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

References (50)

Show source-provided references
1. 10.1016/j.cell.2012.03.04210.1016/j.cell.2012.03.042 ↗
2. 10.1038/s41556-021-00818-310.1038/s41556-021-00818-3 ↗
3. 10.1038/nchembio.223910.1038/nchembio.2239 ↗
4. 10.1016/j.cell.2024.01.03010.1016/j.cell.2024.01.030 ↗
5. 10.1038/s41556-019-0305-610.1038/s41556-019-0305-6 ↗
6. 10.1073/pnas.160324411310.1073/pnas.1603244113 ↗
7. 10.1038/nchembio.223810.1038/nchembio.2238 ↗
8. 10.1016/j.cell.2023.05.00310.1016/j.cell.2023.05.003 ↗
9. 10.1016/j.cell.2013.12.01010.1016/j.cell.2013.12.010 ↗
10. 10.1038/s41586-019-1707-010.1038/s41586-019-1707-0 ↗
11. 10.1038/s41586-021-03539-710.1038/s41586-021-03539-7 ↗
12. 10.1038/s41589-020-0613-y10.1038/s41589-020-0613-y ↗
13. 10.1002/advs.20220400610.1002/advs.202204006 ↗
14. 10.1038/s42003-023-05477-810.1038/s42003-023-05477-8 ↗
15. 10.1038/s41586-019-1705-210.1038/s41586-019-1705-2 ↗
16. 10.1038/s41586-023-06983-910.1038/s41586-023-06983-9 ↗
17. 10.1038/ncb306410.1038/ncb3064 ↗
18. 10.1038/s41586-022-05022-310.1038/s41586-022-05022-3 ↗
19. 10.1016/j.apsb.2022.02.00310.1016/j.apsb.2022.02.003 ↗
20. 10.1111/liv.1442810.1111/liv.14428 ↗
21. 10.1016/j.cmet.2024.07.01310.1016/j.cmet.2024.07.013 ↗
22. 10.1161/CIRCULATIONAHA.122.06025710.1161/CIRCULATIONAHA.122.060257 ↗
23. 10.1073/pnas.182102211610.1073/pnas.1821022116 ↗
24. 10.1016/j.redox.2024.10314510.1016/j.redox.2024.103145 ↗
25. 10.1038/s41467-021-24712-610.1038/s41467-021-24712-6 ↗
26. 10.1016/j.cmet.2023.02.00610.1016/j.cmet.2023.02.006 ↗
27. 10.1016/j.bioorg.2024.10726110.1016/j.bioorg.2024.107261 ↗
28. 10.1038/s41420-024-02127-810.1038/s41420-024-02127-8 ↗
29. 10.2165/00003495-200565070-0000810.2165/00003495-200565070-00008 ↗
30. 10.1016/S2352-4642(22)00239-510.1016/S2352-4642(22)00239-5 ↗
31. 10.3390/cells1207105010.3390/cells12071050 ↗
32. 10.1080/21655979.2021.199599410.1080/21655979.2021.1995994 ↗
33. 10.1016/j.isci.2021.10264910.1016/j.isci.2021.102649 ↗
34. 10.1074/jbc.M117.79840510.1074/jbc.M117.798405 ↗
35. 10.1186/s40880-018-0288-x10.1186/s40880-018-0288-x ↗
36. 10.1016/0049-3848(86)90057-510.1016/0049-3848(86)90057-5 ↗
37. 10.1016/j.ejmech.2018.03.04610.1016/j.ejmech.2018.03.046 ↗
38. 10.1016/S0024-3205(00)00502-610.1016/S0024-3205(00)00502-6 ↗
39. 10.1038/nrgastro.2015.20010.1038/nrgastro.2015.200 ↗
40. 10.1038/s41575-021-00549-810.1038/s41575-021-00549-8 ↗
41. 10.1038/mp.2017.17110.1038/mp.2017.171 ↗
42. 10.7150/thno.10231810.7150/thno.102318 ↗
43. 10.1016/j.cmet.2024.09.00710.1016/j.cmet.2024.09.007 ↗
44. 10.1038/s41569-022-00735-410.1038/s41569-022-00735-4 ↗
45. 10.1038/s41392-024-01962-610.1038/s41392-024-01962-6 ↗
46. 10.1016/j.molcel.2015.06.01110.1016/j.molcel.2015.06.011 ↗
47. 10.1016/j.freeradbiomed.2018.09.01410.1016/j.freeradbiomed.2018.09.014 ↗
48. 10.1038/nature1434410.1038/nature14344 ↗
49. 10.1038/s41556-018-0178-010.1038/s41556-018-0178-0 ↗
50. 10.3390/antiox1112244410.3390/antiox11122444 ↗