| CAS |
No.371131-16-7 |
| 英文名称 |
PZ-128 |
| 分子式 |
C55H99N13O9 |
| 分子量 |
1086.46 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:-20℃，1 year;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD32874091 |
| SMILES |
CCCCCCCCCCCCCCCC(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CO)C(=O)NC(CCCN=C(N)N)C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(CC1=CC=CC=C1)C(=O)N |
| InChIKey |
VZRIKWNVDCTBTF-BKGFHLQYSA-N |
| InChI |
InChI=1S/C55H99N13O9/c1-5-6-7-8-9-10-11-12-13-14-15-16-20-31-47(70)63-41(28-21-23-32-56)51(74)64-42(29-22-24-33-57)52(75)68-46(37-69)54(77)65-43(30-25-34-61-55(59)60)50(73)62-39(4)49(72)67-45(35-38(2)3)53(76)66-44(48(58)71)36-40-26-18-17-19-27-40/h17-19，26-27，38-39，41-46，69H，5-16，20-25，28-37，56-57H2，1-4H3，(H2，58，71)(H，62，73)(H，63，70)(H，64，74)(H，65，77)(H，66，76)(H，67，72)(H，68，75)(H4，59，60，61)/t39-，41-，42-，43-，44-，45-，46-/m0/s1 |
| PubChem CID |
72187679 |
| 靶点 |
PAR1 |
| 通路 |
GPCR & G Protein |
| 背景说明 |
PZ-128是一种特异性的且可逆的PAR1拮抗剂。PZ-128 具有抗血小板，抗转移，抗血管生成和抗癌活性。 |
| 生物活性 |
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].Animal Model: Female NCR Nu/Nu mice (5-7 weeks) injected with OVCAR-4 or SKOV-3 cells[1]；Dosage:10 mg/kg；Administration:Intraperitoneal injection; every other day; for 6 weeks；Result: Significantly reduced mean ascites fluid volume by 60%. |
| 数据来源文献 |
[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. |
| 规格 |
5mg 10mg 25mg |
| 单位 |
瓶 |
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