| Bioactivity | 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]. | ||||||
| Invitro | 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]. Animal Model: | ||||||
| Name | PZ-128 | ||||||
| CAS | 371131-16-7 | ||||||
| Shortening | {Palmitate}-KKSRALF-NH2 | ||||||
| Formula | C55H99N13O9 | ||||||
| Molar Mass | 1086.46 | ||||||
| Appearance | Solid | ||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||
| Storage | Sealed storage, away from moisture
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
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| Reference | [1]. Anika Agarwal, et al. Targeting a metalloprotease-PAR1 signaling system with cell-penetrating pepducins inhibits angiogenesis, ascites, and progression of ovarian cancer. Mol Cancer Ther. 2008 Sep;7(9):2746-57. [2]. Lidija Covic, et al. Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach. Int J Mol Sci. 2018 Jul 31;19(8):2237. [3]. Ping Zhang, et al. Suppression of arterial thrombosis without affecting hemostatic parameters with a cell-penetrating PAR1 pepducin. Circulation. 2012 Jul 3;126(1):83-91. [4]. Paul A Gurbel, et al. Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2016 Jan;36(1):189-97. |