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SN-6109 was further tested in mice, showing efficacy against TNF-α-induced systemic inflammatory response syndrome. In conclusion, a phenotypic-driven HTS cascade promptly identified robust necroptosis inhibitors with in vivo activity, currently undergoing further medicinal chemistry optimization. Notably, the novel hits highlight the opportunity to identify new molecular mechanisms of action in necroptosis. © The Author(s) 2020.Nuclear factor 90 (NF9, an RNA-binding protein, has been implicated in regulating interleukin-2 (IL-2) and
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