PZ-128(P1pal-7)是一种细胞穿透肽，是一种首创的，特异性的且可逆的蛋白酶激活受体1(PAR1)拮抗剂。PZ-128靶向血小板内表面上的受体-G-蛋白(receptor-G-protein)界面。PZ-128具有抗血小板，抗转移，抗血管生成和抗癌作用。
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 receptor-G-protein interface on the inside surface of platelets. PZ-128 has antiplatelet, anti-metastatic, anti-angiogenic and anticancer effects[1][2][3][4].
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 (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: Female NCR Nu/Nu mice (5-7 weeks) injected with OVCAR-4 or SKOV-3 cells[1]
[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.
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