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- W3143175998 abstract "Cisplatin (cis-dichloro-diammine platinum, CDDP) is a well-known chemotherapeutic drug against a broad spectrum of human malignancies. However, the clinical utility of this effective chemotherapy agent is dose limited by its toxic side effects such as nephrotoxicity and ototoxicity. Necroptosis is a form of programmed necrotic cell death that is mediated by serine/threonine kinases, RIPK1 and RIPK3, together with MLKL. In this study, we identified that the multitargeted kinase inhibitor KW-2449 inhibited cisplatin-induced necroptosis, while potentiated cisplatin-induced apoptosis in cancer cells. Mechanistic studies indicated that KW-2449 directly inhibited RIPK1 kinase activity to block necroptosis. Oral administration of KW-2449 attenuated renal cell necrosis and reduced pro-inflammatory responses in mouse models of cisplatin-induced nephrotoxicity. Taken together, our study shows that KW-2449 is a novel necroptosis inhibitor by targeting RIPK1 kinase activity and has great clinic potential for the treatment of cisplatin-induced nephrotoxicity." @default.
- W3143175998 created "2021-04-13" @default.
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- W3143175998 date "2021-06-01" @default.
- W3143175998 modified "2023-10-16" @default.
- W3143175998 title "The multitargeted kinase inhibitor KW-2449 ameliorates cisplatin-induced nephrotoxicity by targeting RIPK1-mediated necroptosis" @default.
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- W3143175998 doi "https://doi.org/10.1016/j.bcp.2021.114542" @default.
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