Pre-clinical studies using RIPK1 kinase dead mice and the first generation indole-hydantoin RIP1 kinase inhibitors, Necrostatin-1s (Nec-1s), and less-specific analogue Nec-1, have demonstrated the potential to target RIPK1 signalling in numerous injury (e.g., renal ischaemic reperfusion, hypoxic brain injury), acute (e.g., systemic inflammatory response syndrome), and chronic inflammatory disease models (e.g., multiple sclerosis) (comprehensively reviewed in [42,94,101]). This evidence concerns the gene RIPK1 and systemic inflammatory response syndrome.