Structure-based optimizations of a necroptosis inhibitor (SZM594) as novel protective agents of acute lung injury
Graphical abstract
A series of derivatives of SZM594 were synthesized based on a structure-based design strategy. The cyclohexanone-containing analogue 41 improved the selectivity toward receptor-interacting protein kinase 1 (RIPK1) over RIPK3 and increased the anti-necroptosis activity and significantly alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a mouse model.
Section snippets
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was funded by grants from the National Natural Science Foundation of China (Nos. 82022065, 81872791, 82073696, 81872880 and U20A20136); the Key Research and Development Program of Ningxia (No. 2019BFG02017, China); the Scientific and Technological Innovation Project of Science and Technology Commission of Shanghai Municipality (No. 21S11900800, China).
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These authors contributed equally to this work.