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| Targets |
PNC-28 targets the p53-mdm-2 interaction by mimicking the N-terminal transactivation domain of the p53 protein. The peptide sequence contains the mdm-2 binding domain (residues 17-26) of p53, allowing it to bind to the mdm-2 oncoprotein. By competing with endogenous p53 for mdm-2 binding, PNC-28 can potentially reactivate p53 tumor suppressor function in cancer cells. The penetratin sequence facilitates cellular uptake, enabling intracellular access to the p53/mdm-2 pathway.
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| ln Vitro |
The proliferation of deadly human pancreatic cancer cell lines is inhibited by PNC-28 (0-0.5 mg/mL) [2].
In vitro, PNC-28 acetate at concentrations ranging from 0-0.5 mg/mL inhibits the growth of lethal human pancreatic cancer cell lines. The peptide exhibits cytotoxic activity against cancer cells, blocking pancreatic cancer cell growth in culture systems. Detailed mechanistic studies demonstrate that PNC-28 induces apoptosis in cancer cells by activating p53-mediated cell death pathways. The penetratin sequence ensures efficient intracellular delivery of the p53 mimetic peptide to reach its molecular targets. |
| ln Vivo |
For 14 days, PNC-28 (2 mg/mouse, SC or IP) inhibits BMRPA1 proliferation in vivo [1]. The growth of BMRPA1 Tuc3 tumors is inhibited by PNC-28 (1–20 mg/mouse, SC, for 14 days) [1].
In vivo, PNC-28 administered subcutaneously (SC) or intraperitoneally (IP) at a dose of 2 mg/mouse for 14 days effectively inhibited the in vivo growth of BMRPA1 tumors in mouse xenograft models. At a dosage range of 1-20 mg/mouse given SC over 14 days, PNC-28 also suppressed the growth of BMRPA1 Tuc3 tumors. These results demonstrate the in vivo anti-tumor efficacy of PNC-28 in pancreatic cancer models. The peptide is administered as a solution in an appropriate vehicle such as 5% DMSO/30% PEG300/5% Tween 80/60% saline for injections. |
| Enzyme Assay |
A typical in vitro cell viability assay is performed using human pancreatic cancer cell lines (e.g., Panc-1, BxPC-3, or BMRPA1). Cells are seeded in 96-well plates (5,000-10,000 cells/well) in RPMI-1640 or DMEM supplemented with 10% FBS. After 24 h of attachment, cells are treated with varying concentrations of PNC-28 acetate (0-0.5 mg/mL, serially diluted) for 48-72 h. Cell viability is measured using MTT or CellTiter-Glo luminescent assay. The IC50 values are calculated by fitting a sigmoidal dose-response curve. Apoptosis can be confirmed by Annexin V-FITC/PI staining and flow cytometry, or by measuring caspase-3/7 activity. For receptor binding studies, no specific protocol is available for this peptide.
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| Cell Assay |
Human pancreatic cancer cell lines are cultured in appropriate media at 37degC in a 5% CO2 humidified incubator. Cells are seeded in 96-well plates at a density of 5,000 cells per well. After 24 h, the culture medium is replaced with fresh medium containing PNC-28 acetate (0.01-0.5 mg/mL). Cells are incubated for 48-72 h. Cell viability is assessed using the MTT assay: add 10 microL of MTT solution (5 mg/mL) to each well, incubate for 4 h, then add 100 microL of DMSO to dissolve formazan crystals. Absorbance is measured at 570 nm using a microplate reader. Apoptosis is evaluated by Hoechst 33342 staining to visualize nuclear condensation and fragmentation, or by performing a TUNEL assay following the manufacturer's protocol.
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| Animal Protocol |
Female BALB/c nude mice (5-6 weeks, 18-20 g, n=6-8 per group) are implanted subcutaneously with 2-5 × 10⁶ BMRPA1 or BMRPA1 Tuc3 pancreatic cancer cells suspended in 100 microL PBS/Matrigel. When tumors reach approximately 50-100 mm3, mice are randomized and treated with PNC-28 acetate (1-20 mg/mouse, administered SC or IP in 100-200 microL of sterile PBS) daily for 14 days. Control groups receive vehicle (PBS) or an irrelevant control peptide. Tumor volume is measured every 2-3 days using a digital caliper, calculated as (length × width2)/2. Body weight is monitored as a general toxicity indicator. At the end of the treatment period, mice are euthanized, and tumors are excised, weighed, and processed for histology (H&E) and immunohistochemistry (e.g., Ki-67 for proliferation, cleaved caspase-3 for apoptosis). Pharmacodynamic markers such as p53, mdm-2, and p21 levels in tumor lysates can be assessed by Western blot.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are available for PNC-28 acetate. As a 29-amino acid peptide (molecular weight approximately 3569.18 g/mol), PNC-28 is expected to be rapidly degraded by serum proteases following systemic administration, leading to a short half-life (likely less than 30 minutes). The penetratin sequence facilitates cellular entry, but the overall bioavailability in vivo is likely low. For in vivo studies, multiple daily administrations or continuous infusion via an osmotic pump may be considered. The peptide should be dissolved in sterile PBS, 5% DMSO/PBS, or a formulation containing PEG300 and Tween 80 to enhance solubility for injection.
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| Toxicity/Toxicokinetics |
No formal toxicity studies have been reported for PNC-28 acetate. In animal efficacy studies, the compound was generally well-tolerated at doses up to 20 mg/mouse (approximately 500-1000 mg/kg) administered daily for 14 days, with no significant mortality or severe adverse effects reported. As a p53 mimetic peptide, the primary mechanism-based safety concern would be the potential for off-target apoptosis in normal tissues expressing wild-type p53. Long-term safety and formal toxicology studies (e.g., 28-day repeat-dose toxicity, genotoxicity, cardiovascular safety) have not been conducted.
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| References |
[1]. Kelley A. Sookraj. QS304. Novel p53-Derived Peptide Induces Rapid Human Pancreatic Cancer Cell Death. 2008, 144(2), 1.
[2]. Michl J, et al. PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo. Int J Cancer. 2006 Oct 1;119(7):1577-85. |
| Additional Infomation |
PNC-28 acetate is a research-grade peptide and is not approved by the FDA, EMA, or any other regulatory agency for clinical use. It is a p53 peptide derived from the mdm-2-binding domain (residues 17-26) of the p53 protein containing a membrane crossing-penetratin sequence. The penetratin sequence is derived from the Antennapedia homeodomain, enabling the peptide to cross cell membranes efficiently. This product is for research purposes only and not for therapeutic applications. Store as a lyophilized powder at -20degC or below, protected from light.
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| Molecular Formula |
C164H255N47O37S.C2H4O2
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| Related CAS # |
PNC-28;392661-17-5
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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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