GSK484 (hydrochloride)

GSK484 (hydrochloride) (CAS No.: 1652591-81-5) is a selective, reversible small-molecule inhibitor of peptidylarginine deiminase 4 (PAD4), an enzyme that catalyzes the calcium-dependent conversion of arginine residues to citrulline in proteins, a post-translational modification implicated in inflammation, autoimmunity, and cancer. GSK484 binds preferentially to the low-calcium conformation of PAD4 at its active site, thereby blocking enzymatic activity and suppressing protein citrullination, with reported inhibitory potency in the nanomolar range under calcium-depleted conditions and reduced potency at elevated calcium levels. The compound exhibits high selectivity for PAD4 over other PAD isoforms and effectively inhibits PAD4-mediated processes such as the formation of neutrophil extracellular traps in both human and murine systems. Functionally, GSK484 is widely utilized as a chemical probe to investigate PAD4-dependent signaling pathways and the role of citrullination in disease pathogenesis, particularly in studies of inflammatory disorders, autoimmune diseases, and tumor biology. In vitro and in vivo studies indicate that it has favorable pharmacokinetic properties in preclinical species, supporting its use in mechanistic and translational research, with experimental concentrations or dosing regimens varying according to specific assay conditions and study objectives.