| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PZ-128 specifically targets the protease-activated receptor-1 (PAR1), a G protein-coupled receptor involved in platelet activation, inflammation, and cancer progression. It acts as a pepducin, a lipidated peptide that targets the cytoplasmic surface of PAR1. By binding to the intracellular loops of the receptor, it interrupts the signaling to internally-located G proteins (PAR1-G). This mechanism of action is distinct from traditional receptor antagonists that target the extracellular ligand-binding domain.
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| ln Vitro |
Ninety-nine percent of OVCAR-4 migration into human ovarian ascites and fibroblast-conditioned media is blocked by PZ-128 (P1pal-7; 3 μM). PZ-128 nearly entirely reduced the 2.2-fold increase in endothelial barrier permeability seen in conditioned media of peritoneal fibroblasts treated with OVCAR4 [1]. Targeting the cytoplasmic surface of PAR1, PZ-128 is a lipidated "pepducin" that obstructs internal G protein signaling. PZ-128's structure was discovered to replicate the closed state of PAR1's equivalent intracellular region, which is essential for coupling to G proteins [3].
In vitro, PZ-128 exhibits antiplatelet, anti-metastatic, and anti-angiogenic activities. Its ability to inhibit platelet aggregation is a key feature, as it suggests a potential role in preventing thrombosis. Its anti-metastatic and anti-angiogenic effects are relevant for its potential as an anticancer agent. These activities have been demonstrated in various cell-based assays. Specific IC50 values are not detailed in the available literature. |
| ln Vivo |
PZ-128 (P1pal-7; 10 mg/kg; intraperitoneal injection; every other day; for 6 weeks) treatment significantly reduced mean ascites volume by 60%. PZ-128 treatment also resulted in a significant 84-96% reduction in vessel density in the center and edges of OVCAR-4 tumors [1].
In vivo, PZ-128 has shown anticancer effects and antiplatelet activity in research models. Its ability to inhibit platelet aggregation suggests it could be effective in preventing arterial thrombosis. Its anti-metastatic and anti-angiogenic activities suggest it could inhibit tumor growth and spread. However, specific in vivo data, such as its efficacy in particular animal models, is not detailed in the available summaries. |
| Enzyme Assay |
Cell-free assays for PZ-128 are not the primary method for characterizing its activity, as it is a pepducin that targets the intracellular surface of a receptor. Its binding to PAR1 could be studied using biophysical techniques like surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) using purified PAR1 protein or peptides corresponding to the intracellular loops. However, the functional readout of its activity is typically assessed in cell-based or in vivo assays.
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| Cell Assay |
In vitro cell-based assays for PZ-128 are performed to study its effects on PAR1 signaling. Cells expressing PAR1 are treated with the compound, and the inhibition of downstream signaling pathways is measured. For example, PAR1 activation leads to the release of calcium from intracellular stores and the activation of various kinases. The effect of PZ-128 on these signaling events can be measured using calcium-sensitive dyes or by Western blotting for phosphorylated signaling proteins. Platelet aggregation assays are also used to measure its functional effect.
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| Animal Protocol |
Animal/Disease Models: Female NCR Nu/nu (nude) mice (5-7 weeks) injected with OVCAR-4 or SKOV-3 cells [1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; every other day; for 6 weeks Experimental Results: The average ascites volume was Dramatically diminished by 60%. In vivo animal experiments for PZ-128 would involve models of thrombosis, cancer, or metastasis. For thrombosis studies, a model of arterial thrombosis (e.g., the ferric chloride-induced carotid artery thrombosis model) could be used. The compound would be administered, and the time to occlusion or the reduction in thrombus formation would be measured. For cancer studies, xenograft or metastasis models would be used to assess the compound's effect on tumor growth and spread. Specific protocols are not detailed in the available literature. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for PZ-128 is not provided in the available literature. As a lipopeptide, its properties, such as bioavailability and half-life, would be important for its development. Its cell-penetrating nature suggests it has the ability to cross cell membranes. For storage, the compound is typically kept as a powder.
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| Toxicity/Toxicokinetics |
Toxicological data for PZ-128 is not available in the public literature. As a research compound, its safety profile would be a critical factor in its development. However, no specific LD50, organ toxicity, or genotoxicity data are reported. Its use is strictly for research purposes, and it is not intended for human therapeutic use.
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| References |
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| Additional Infomation |
PZ-128 has been used in trials to study the prevention and treatment of diseases such as heart disease, coronary artery disease, arteriosclerosis, vascular disease, and myocardial ischemia.
PZ-128 is a research-grade compound developed as a first-in-class PAR1 antagonist with a unique mechanism of action. It is a valuable tool for studying the role of PAR1 in platelet function, inflammation, and cancer. Its ability to target the intracellular surface of the receptor makes it a novel type of therapeutic agent. It has not been approved for clinical use. All information is for research reference and not for diagnostic or clinical use. |
| Molecular Formula |
C55H99N13O9
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| Molecular Weight |
1086.47
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| Exact Mass |
1085.768
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| CAS # |
371131-16-7
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| PubChem CID |
72187679
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.585
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| LogP |
4.95
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| Hydrogen Bond Donor Count |
13
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
45
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| Heavy Atom Count |
77
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| Complexity |
1750
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CCCCCCCCCCCCCCCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N
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| InChi Key |
VZRIKWNVDCTBTF-BKGFHLQYSA-N
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| InChi Code |
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
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| Chemical Name |
N-[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]hexadecanamide
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| Synonyms |
PZ 128 PZ128 PZ-128
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~92.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9204 mL | 4.6021 mL | 9.2041 mL | |
| 5 mM | 0.1841 mL | 0.9204 mL | 1.8408 mL | |
| 10 mM | 0.0920 mL | 0.4602 mL | 0.9204 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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