产品描述:
GSK 199 is an inhibitor of peptidyl arginine deiminase 4 (PAD4; IC50 = 200 nM in the absence of calcium).{28376} It selectively inhibits the production of citrulline by PAD4 over PAD1, PAD2, and PAD3 in kinetic assays. GSK 199 (10 µM) prevents histone H3 citrullination and neutrophil extracellular trap (NET) formation induced by ionomycin (Item No. 10004974) in isolated mouse peripheral blood neutrophils. It reduces human coronavirus OC43 (HCoV-OC43) replication in infected MRC-5 cells (IC50 = 0.6 µM).{66768} In vivo, GSK 199 (10 and 30 mg/kg) reduces complement C3 deposition in the synovium and cartilage but does not reduce total synovial or serum citrulline levels in a mouse model of collagen-induced arthritis.{34700} It reduces disease severity in the same model when administered at a dose of 30 mg/kg. GSK 199 (30 mg/kg) also reduces plasma NET levels and brain infarct volume, as well as improves neurological outcomes, in a mouse model of ischemic stroke induced by transient middle cerebral artery occlusion (tMCAO).{66769}