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- W4212851421 abstract "Background: Necroptosis is an important form of regulated cell death involved in inflammatory diseases, degenerative diseases and cancer. RIPK3 is an interesting target for intervention of necroptosis-associated diseases. Methodology: Herein the authors report the synthesis of a series RIPK3 inhibitors under the guidance of structure-based drug design which leads to the identification of compound 37. Results: Compound 37 potently rescued human and mouse cells from necroptotic stimuli TNF-α, Smac mimetic, z-VAD and LPS + z-VAD, displayed high affinity to RIPK3 (Kd = 14 nM) but no observable affinity to RIPK1 and inhibited RIPK3 kinase function. Importantly, compound 37 significantly alleviated TNF-induced systemic inflammatory response syndrome in the mouse model. Conclusion: These results support compound 37 as a prototype RIPK3 inhibitor for lead optimization." @default.
- W4212851421 created "2022-02-24" @default.
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- W4212851421 date "2022-02-15" @default.
- W4212851421 modified "2023-10-18" @default.
- W4212851421 title "Synthesis and characterization of potent RIPK3 inhibitors based on a tricyclic scaffold" @default.
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- W4212851421 doi "https://doi.org/10.4155/fmc-2021-0196" @default.
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