| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Pep2-8 directly targets PCSK9 by binding to its EGF(A) domain-binding site, thereby preventing PCSK9 from interacting with the LDLR. By blocking the PCSK9-LDLR interaction, Pep2-8 increases LDLR surface levels and enhances LDL particle uptake. The peptide also downregulates PCSK9-mediated inflammatory processes, including NOX4, MAPK subunits, and NF-kappaB expression, thereby targeting vascular aging mechanisms.
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| ln Vitro |
PCSK9 with a shortened C-terminus is bound by Pep2-8 TFA[1]. In HepG2 cells treated with PCSK9, Pep2-8 TFA restored LDL uptake to almost 90% of control activity at a dose of 50 μM [1].
In HepG2 cells treated with exogenous PCSK9, Pep2-8 (5-50 uM) fully restores LDL receptor surface levels and LDL particle uptake. The peptide treatment also markedly restores efferocytosis in endothelium from aged mice. A proteomics study in the aortic arch of aged mice reveals that Pep2-8 significantly downregulates expression of NOX4, MAPK subunits, NF-kappaB, and pro-inflammatory cytokines such as IL-6 and TNF-alpha. |
| ln Vivo |
In male Wistar rats subjected to cardiac ischemia/reperfusion injury, intravenous administration of Pep2-8 (10 microg/kg) prior to ischemia significantly reduces infarct size, improves left ventricular function, attenuates cardiac arrhythmia, and protects cardiac mitochondrial function. PCSK9 is upregulated in ischemic hearts, and its inhibition by Pep2-8 limits infarct size. In aged mice, Pep2-8 treatment improves vascular function by suppressing the PCSK9/NOX4/NF-kappaB axis.
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| Enzyme Assay |
Phage-display screening is employed to identify peptides that bind to recombinant PCSK9 protein. Surface plasmon resonance (SPR) or ELISA-based binding assays are used to measure the direct binding affinity of Pep2-8 to immobilized PCSK9. A competitive binding assay using biotinylated EGF(A) domain and labeled PCSK9 is performed, where increasing concentrations of Pep2-8 displace the EGF(A) signal, indicating binding to the same site on PCSK9. Dose-response curves yield IC50 values.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: HepG2 cell. Tested Concentrations: 15 μg/mL. Incubation Duration: 4 h. Experimental Results: Inhibited PCSK9 activity. HepG2 cells are treated with exogenous recombinant human PCSK9 (1-5 microg/mL) in the presence or absence of increasing concentrations of Pep2-8 (ranging from 1-100 uM) for 4-6 hours. After treatment, cells are harvested and surface LDLR expression is analyzed by flow cytometry using an anti-LDLR antibody. Alternatively, cellular LDL uptake is measured using fluorescently labeled Dil-LDL (5-10 microg/mL) and quantified by fluorescence microscopy or flow cytometry. |
| Animal Protocol |
Male Wistar rats (250-300 g) are subjected to left anterior descending coronary artery ligation to induce cardiac I/R injury (30 min ischemia followed by 2 h reperfusion). Pep2-8 (10 microg/kg in 0.9% saline) is administered intravenously as a bolus at different time points: 10 min before ischemia, during ischemia (just before reperfusion), or at the onset of reperfusion. Infarct size is determined by triphenyltetrazolium chloride staining. Left ventricular function is measured via a pressure-volume catheter inserted into the LV. Arrhythmia scores are calculated. Mitochondrial function is assessed in isolated cardiac mitochondria by measuring respiratory control ratio (state 3/state 4) using a Clark-type oxygen electrode. For aged mouse studies (24-month-old C57BL/6 mice, n=5-8 per group), Pep2-8 is administered via tail vein injection (dose from literature, typically 0.1-1 mg/kg), and aortic arches are collected for proteomic analysis, efferocytosis assays, and immunohistochemistry.
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| ADME/Pharmacokinetics |
Detailed quantitative PK data for Pep2-8 are not available. As a 13-aa linear peptide, its plasma half-life is expected to be very short (likely <30 min) due to rapid degradation by serum proteases. In rats, Pep2-8 shows efficacy when given intravenously prior to ischemia, but is ineffective when given during or after ischemia, likely reflecting the need for high initial plasma concentration and rapid clearance. For in vivo experiments, peptide should be dissolved in sterile saline or PBS and administered immediately.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for Pep2-8. In animal studies, no adverse effects on survival or behavior were noted at the doses used (10 microg/kg in rats). Given that the peptide is designed to block the PCSK9/LDLR interaction, the primary mechanism-based safety concern would be very low LDL cholesterol, a condition that is generally well-tolerated. However, long-term toxicity studies have not been conducted.
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| References | |
| Additional Infomation |
Pep2-8 is strictly a research tool and is not FDA-approved for human therapy. It is one of the earliest described peptide inhibitors of PCSK9 and continues to be used as a template for designing more potent, stabilized peptide therapeutics. Modifications such as stapled peptides or self-assembling domains (EPep2-8) have been developed to improve its bioavailability and in vivo stability. The TFA salt is the standard formulation for cell culture and animal studies.
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| Molecular Formula |
C85H111F3N16O26
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| Molecular Weight |
1715.85 (free base)
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| Related CAS # |
Pep2-8;1541011-97-5
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| Appearance |
White to off-white solid powder
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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