GSK199 (hydrochloride)

GSK199 (hydrochloride) (CAS No.: 1549811-53-1) is a small-molecule, orally active, reversible, and selective inhibitor of peptidyl arginine deiminase 4 (PAD4), an enzyme that catalyzes protein citrullination and plays a critical role in the regulation of inflammatory and autoimmune processes. By directly binding to PAD4 and inhibiting its enzymatic activity, GSK199 effectively reduces the conversion of arginine residues to citrulline, thereby modulating downstream signaling pathways associated with neutrophil extracellular trap formation, chromatin decondensation, and inflammatory mediator production. The compound demonstrates inhibitory activity in the nanomolar range under calcium-free conditions and exhibits marked selectivity over other PAD isoforms, supporting its utility in dissecting PAD4-specific biological functions. In cellular systems, GSK199 suppresses histone H3 citrullination and inhibits NET formation in activated neutrophils, while also showing antiviral effects in certain infected cell models at low micromolar concentrations. In vivo studies indicate that it can attenuate inflammatory pathology, reduce complement deposition, and improve disease-related outcomes in models of autoimmune arthritis and ischemic injury, without broadly altering systemic citrulline levels. GSK199 (hydrochloride) is therefore widely used as a pharmacological tool in studies of epigenetic regulation, innate immunity, and inflammatory disease mechanisms, with experimental concentrations or dosing regimens typically optimized according to specific cell-based assays or animal model designs.