RIPA-56

RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of Receptor-Interacting Protein 1 (RIP1) kinase with an IC₅₀ of 13 nM. It protects HT-29 cells against TNFα-induced necroptosis with an EC₅₀ of 28 nM. RIPA-56 efficiently reduces TNFα-induced mortality and multiorgan damage in a systemic inflammatory response syndrome (SIRS) mice model. Modulators of RIP kinase 1 may be beneficial against SARS-CoV-2 based on interaction of RIP kinase 1 with SARS-CoV-2 protein Nsp12.