PZ-128

PZ-128 (P1pal-7), a cell-penetrating lipopeptide pepducin, is a first-in-class, specific and reversible protease-activated receptor-1 (PAR1) antagonist. PZ-128 targets the cytoplasmic surface of PAR1 and interrupts signaling to internally-located G (PAR1-G) proteins. PZ-128 has antiplatelet, anti-metastatic, anti-angiogenic and anticancer effects^[1][2][3][4]. In Vitro: PZ-128 (P1pal-7; 3 μM) blocks 90-94% of OVCAR-4 migration toward human ovarian ascites and fibroblast conditioned media. The OVCAR4-treated peritoneal fibroblast conditioned media elicits a 2.2-fold increase in endothelial barrier permeability which could be nearly completely inhibited by PZ-128^[1].
PZ-128 is a lipidated ‘pepducin’ which targets the cytoplasmic surface of PAR1 and interrupts signaling to internally-located G proteins. The structure of PZ-128 is found to mimic the off-state of the corresponding intracellular region of PAR1 which is critical for coupling to G proteins^[3]. In Vivo: PZ-128 (P1pal-7; 10 mg/kg; intraperitoneal injection; every other day; for 6 weeks) treatment significantly reduces mean ascites fluid volume by 60%. PZ-128 treatment also causes a highly significant 84-96% reduction in blood vessel density in both the center and edge of the OVCAR-4 tumors^[1].