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PNC-27

● Preclinical
PNC-27, Anticancer p53-HDM2 Binding Peptide
Also known as: PNC27, p53 peptidomimetic, MDM2 antagonist peptide
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Quick Summary

PNC-27 is a synthetic peptide containing the p53 HDM2-binding domain linked to a transmembrane sequence. In cancer cells, HDM2 (the human homolog of MDM2) is frequently overexpressed and sequesters p53, preventing apoptosis.

Experimental / Oncology Research Preclinical
PNC-27 is a synthetic peptide containing the p53 HDM2-binding domain linked to a transmembrane sequence. In cancer cells, HDM2 (the human homolog of MDM2) is frequently overexpressed and sequesters p53, preventing apoptosis. PNC-27 targets cells expressing HDM2 on their plasma membrane surface (a characteristic of many cancer cells but not normal cells), inserts into their membrane, and creates pores that cause rapid cell death. Normal cells without surface HDM2 are largely unaffected, providing cancer selectivity.
Storage Stability
Lyophilized
1–2 years (-20°C)
Reconstituted
~30 days (2–8°C)
Room temp
Avoid

Mechanism of Action

HDM2 Surface Targeting

Many cancer cell types express HDM2 on their external plasma membrane surface, an aberrant localization not seen in normal cells. PNC-27's p53 domain binds this surface HDM2, concentrating the peptide on cancer cells.

Membrane Pore Formation

The transmembrane penetratin sequence in PNC-27 then inserts into the lipid bilayer, oligomerizes, and forms pores. These pores disrupt membrane integrity, causing rapid necrotic/apoptotic cell death.

Selectivity

The selectivity for cancer cells depends on surface HDM2 expression. Cell lines with high surface HDM2 (pancreatic, breast, melanoma) show high sensitivity; normal cell lines are largely spared.

Research Summary

In Vitro Data

PNC-27 kills numerous cancer cell lines including pancreatic (MiaPaCa-2), breast, leukemia, and melanoma lines within hours of treatment at low micromolar concentrations. Normal cell lines show minimal toxicity.

Pancreatic Cancer Focus

Pancreatic cancer is notoriously resistant to chemotherapy. PNC-27 has shown particular promise in this indication where surface HDM2 expression is consistently high.

Animal Models

Limited but encouraging xenograft data shows tumor growth inhibition with PNC-27 treatment in mouse models without significant systemic toxicity.

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Research Protocols

Note: PNC-27 is in early preclinical research. No human dosing data exists.

Cell Culture

In vitro research typically uses 10–100 µM concentrations. Cell viability measured at 24–72 hours.

Animal Models

Intraperitoneal or intratumoral injection in xenograft models. Dose varies by model (see published protocols).

Storage & Handling

Store at -20°C. Reconstitute with DMSO (for cell culture stocks) or sterile saline (animal models). DMSO stock: -80°C long-term. Aqueous solutions: use within 24-48 hours at 4°C.


References

  • [1]Bowne WB, et al. "Anticancer activity of the p53 peptidomimetic PNC-27 against pancreatic cancer." Cancer Res, 2008.
  • [2]Ambrosone A, et al. "PNC-27, a selective apoptosis-inducing peptide in cancer cells." Anticancer Res, 2018.
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Verified Scientific Data Last audited:
Data Sources & External References
Source: peer-reviewed literature  ·  Domain: ascendpeptide.org
PNC-27
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