Biochem/physiol Actions

BB-Cl-amidine is an irreversible pan-protein-arginine deiminase (PAD) inhibitor (k_inact/KI in M^-1min^-1 = 16100/PAD1, 4100/PAD2, 6800/PAD3, 13300/PAD4) with >20-fold increased potency against U2OS osteosarcoma cutlures (viability assay IC50 = 8.8 µM vs >200 µM with Cl-amidine) and longer in vivo half-life (1.75 hrs vs 15 min for Cl-amidine in plasma post injection in mice) than Cl-amidine. BB-Cl-amidine effectively inhibits PMA-induced neutrophils extracellular trap (NET) formation from lupus-prone MRL/lpr mice-derived bone marrow neutrophils in cultures (by 78% and 34% with 20 µM BB-Cl-amidine or Cl-amidine, respectively), while daily s.c. injection (1 mg/kg) is efficacious in ameliorating lupus symptoms in in MRL/lpr mice in vivo.