GSKμ843 is a potent ATP-competitive RIP3 (RIPK3) kinase inhibitor (IC50 = 6.5 nM) with much reduced or little affinity toward 262 other kinases (IC50 >1 μM against 10 μM ATP in competitive binding assay), including RIP5. GSKμ843 effectively suppresses TNF/Z-VAD-FMK/IAP agonist treatment-induced necrosis induction in both human and murine cell cultures (EC50 ranges from <0.12 to 3 μM), while inducing apoptosis in the absence of caspase inhibitor as a result of caspase 8 activation via RHIM-driven recruitment to assemble a Casp8-FADD-cFLIP complex independent of pronecrotic kinase activities and MLKL.