GSK872

GSK872 (CAS No.: 1346546-69-7) is a potent and highly selective small-molecule inhibitor of receptor-interacting protein kinase 3 (RIPK3), a critical regulator of necroptosis, a programmed form of necrotic cell death implicated in inflammation and tissue injury. This compound directly binds to the RIPK3 kinase domain and suppresses its catalytic activity with high potency in the low nanomolar range, exhibiting strong selectivity over a broad panel of kinases. By inhibiting RIPK3 signaling, GSK872 effectively blocks necroptotic pathways triggered by tumor necrosis factor, viral stimuli, and toll-like receptor activation, leading to reduced downstream events such as HMGB1 expression and cytoplasmic translocation. Functionally, GSK872 has been widely utilized in cellular systems, including fibroblast models, to dissect mechanisms of regulated necrosis and inflammatory signaling, and in vivo studies have demonstrated its capacity to attenuate brain edema and improve neurological outcomes in models of acute brain injury. As a research tool, it is extensively applied in studies of cell death, neuroinflammation, and immune-mediated tissue damage, with experimental concentrations or dosing regimens varying depending on specific assay conditions and study objectives.