Description

Product Description

PNC-28 (CAS 392661-17-5) is a synthetic peptide originally engineered from the mdm-2-binding domain (residues 17–26) of the tumor suppressor protein p53, conjugated with a penetratin sequence that enables efficient crossing of cellular membranes. The rationale behind its design is based on targeting p53-mdm2 interactions, a central regulatory mechanism in cancer biology.

Background on p53 and MDM2

• p53 is a tumor suppressor protein that regulates the cell cycle, DNA repair, and apoptosis.

• MDM2 is an E3 ubiquitin ligase that binds p53, promoting its degradation and inhibiting its tumor-suppressive activity.

• In many cancers, overexpression of MDM2 leads to functional inactivation of p53, facilitating tumor survival and progression.

PNC-28 interrupts this critical interaction by mimicking the p53 binding motif while incorporating a penetratin sequence for cell entry. Importantly, it demonstrates tumor-selective cytotoxicity, with minimal effects on normal cells.

Research Applications

1. Pancreatic Cancer

   • One of the deadliest cancers with limited treatment options.

   • PNC-28 induces necrosis-like cell death in pancreatic cancer cell lines.

   • Preclinical models demonstrate its potential as a novel therapeutic peptide.

2. Mechanistic Cancer Studies

   • Used to study p53-MDM2 dynamics.

   • Explores mechanisms of membrane disruption, mitochondrial damage, and apoptosis induction.

3. Drug Formulation Research

   • Comparison between free form and acetate salt form:

     • Both exhibit comparable biological activity.

     • Acetate form demonstrates enhanced solubility, stability, and ease of formulation.

4. Broader Oncology Models

   • Beyond pancreatic cancer, PNC-28 has shown activity in breast cancer, glioblastoma, and other malignancies.

   • Serves as a tool compound in cancer biology laboratories.

Product Specifications

Notes

• Supplied in free peptide and acetate salt forms.

• Salt form enhances water solubility and stability.

• For laboratory research use only.

Mechanism of Action

PNC-28 operates primarily via direct disruption of cancer cell membranes and induction of cell death, independent of canonical p53 pathways.

1. Cell Penetration

   • The penetratin sequence facilitates efficient translocation across cancer cell membranes.

   • Cancer cells demonstrate higher uptake due to altered membrane characteristics.

2. Membrane Disruption

   • PNC-28 inserts into the plasma membrane of tumor cells.

   • Leads to membrane destabilization, pore formation, and necrosis-like death.

3. Mitochondrial Damage

   • Induces loss of mitochondrial membrane potential.

   • Promotes release of cytochrome c and subsequent apoptotic cascades.

4. p53-MDM2 Pathway Interference

   • Mimics p53’s MDM2 binding domain, thereby blocking MDM2-mediated degradation of p53.

   • Stabilizes p53 activity, restoring its tumor-suppressor functions.

5. Tumor Selectivity

   • PNC-28 preferentially kills cancer cells while sparing normal cells.

   • Selectivity is attributed to differences in membrane composition between cancer and healthy cells.

6. Comparison of Free vs. Acetate Form

   • Free PNC-28: biologically active, but less stable in aqueous environments.

   • Acetate salt form: retains equal biological activity with superior solubility and shelf-life, making it more practical for experimental applications.

     

Side Effects

Research Observations

• In vitro, PNC-28 demonstrates strong tumor-selective activity with minimal toxicity to normal fibroblasts and epithelial cells.

• In vivo preclinical studies indicate potential for dose-dependent cytotoxic effects.

Potential Research Risks

• May induce off-target membrane disruption at very high concentrations.

• Long-term systemic administration effects remain under investigation.

• Variability in cell line response requires careful optimization of dosing.

Laboratory Safety Notes

• Handle under sterile conditions.

• Not approved for therapeutic use in humans.

• Use appropriate protective equipment.

Disclaimer

This product is intended for research purposes only. PNC-28 is not approved for clinical or diagnostic use in humans.

Keywords

PNC-28, CAS 392661-17-5, p53-derived peptide, MDM2 binding peptide, penetratin fusion peptide, PNC-28 acetate, pancreatic cancer research peptide, tumor-selective cytotoxic peptide.

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