GSK484

GSK484 is a reversible inhibitor of PAD4 (IC₅₀ = 50 nM) that binds to the low-calcium form of the enzyme. It is selective for PAD4 over PAD1-3. GSK484 blocks the citrullination of PAD4 target proteins in human neutrophils and inhibits the formation of neutrophil extracellular traps in both mouse and human neutrophils. It exhibits favorable pharmacokinetic profiles in mouse and rat. See the Structural Genomics Consortium (SGC) website for more information.

GSK484 is a novel selective PAD4 inhibitor.

GSK484 is a potent selective reversible inhibitor of protein arginine deiminase PAD4, an enzyme believed to play a role in granulocyte and macrophage development leading to inflammation and immune response, and overexpressed in many tumors. GSK484 has IC50 values of 50 nM without calcium and 250 nM in the presence of 2 mM calcium. GSK484 showed minimal off-target activity tested against 50 other proteins with no activation across HDACs 1–11 even at 100 μM. GSK484 binds at a different site from the amidines, a conformation of the PAD4 active site where part of the site is reordered to form a β-hairpin.