In vitro activity: When assayed at 1 μM, GSK'872 fails to inhibit most of 300 human protein kinases tested. It fails to inhibit RIP1 kinase when tested directly. GSK'872 blocks TNF-induced necroptosis in a concentration-dependent manner in HT-29 cells. In cell-based assays, there is a 100- to 1000-fold shift in the IC50 compared to the cell-free biochemical assays. GSK'872 also blocks necroptosis in primary human neutrophils isolated from whole blood. GSK'872 inhibits TLR3- or DAI-induced death, two RIP1-independent pathways of necroptosis. It induces caspase activation followed by apoptotic cell death

Kinase Assay: GSK'872 (also known as GSK2399872A, GSK872, or GSK-872) is a potent and selective RIPK3 (receptor interacting protein kinase-3) inhibitor. It has a high binding affinity to the RIP3 kinase domain with IC50 value of 1.8 nM, and it inhibits the kinase activity with an IC50 of 1.3 nM.

Cell Assay: Viability of 3T3-SA cells at 18 h after treatment with TNF in the presence of Z-VAD-fmk in vehicle control (DMSO) or treated with the indicated concentrations of RIP3 kinase inhibitors, GSK'843 or GSK'872 are assayed.