Back to Peptides

PNC-27

Emerging

Anti-Cancer Peptide | p53-HDM-2 Disruptor

Dose Not established - preclinical research only
Frequency Research protocols vary by study
Cycle Not established - no human clinical trials
Storage Refrigerate at 2-8°C
Accumulation Plotter

PNC-27 is an experimental anti-cancer peptide created by a supercomputer at SUNY Downstate Medical Center in 2000. It contains an HDM-2 binding domain from p53 (residues 12-26) linked to a cell-penetrating domain. The peptide selectively kills cancer cells by binding to HDM-2 (MDM2) expressed on cancer cell membranes, forming pores that cause cell necrosis. Critically, PNC-27 has no effect on normal cells because healthy cells don't express HDM-2 on their membranes. Research shows effectiveness against pancreatic cancer, breast cancer, leukemia, and melanoma.

Mechanism of Action

PNC-27 exploits a unique vulnerability of cancer cells: the presence of HDM-2 (human double minute 2, also called MDM2) on their cell surface. The peptide's p53 residues adopt a conformation that binds directly to membrane-bound HDM-2, inducing transmembrane pore formation. This causes rapid tumor cell necrosis (not apoptosis). Additionally, PNC-27 enters cancer cells and disrupts mitochondrial membranes. Normal cells lack surface HDM-2 expression and are completely spared.

Key Benefits

  • Selectively kills cancer cells only
  • No effect on normal healthy cells
  • Induces rapid cancer cell necrosis
  • Works on multiple cancer types
  • Unique membrane pore mechanism
  • Does not require p53 function in target cells
  • Eradicates tumors in mouse models
  • Spares human stem cells
Molecular Weight
~3,500 Da
Type
Chimeric peptide

Cancer Research

  • Pancreatic Cancer

    PNC-27 shows selective cytotoxicity against pancreatic cancer cells in research.

  • Breast Cancer

    Demonstrated effectiveness against breast cancer cell lines.

  • Leukemia

    Induces necrosis of K-562 leukemia cells through HDM-2 binding.

  • Melanoma

    Shows selective targeting of melanoma cells.

Mechanism Studies

  • HDM-2 Expressing Tumors

    Most effective against cancers with high membrane HDM-2 expression.

  • Tumor Selectivity Research

    Model compound for studying cancer-selective therapies.

PNC-27 is currently in preclinical research stages. All dosing data comes from in vitro and animal model studies. No human dosing protocols have been approved. The peptide has shown tumor eradication in nude mice xenograft models.

GoalDoseFrequencyRoute
Research protocolVariable by studyResearch protocolsIP or direct tumor injection (research)

Reconstitution Instructions

Materials Needed:
  • Sterile water or buffer
  • Syringes
  • Sterile work surface
  1. 1 Handle as research chemical
  2. 2 Reconstitute according to research protocol
  3. 3 Store reconstituted solution refrigerated
  4. 4 Use appropriate safety precautions
Chemotherapy agents

Potential for combination therapy being researched.

unknown
Other anti-cancer peptides

Combination studies not yet published.

unknown
Hours

Binding to membrane HDM-2 begins

Hours-Days

Pore formation and cancer cell necrosis

Days-Weeks

Tumor reduction in animal models

Research ongoing

Human clinical trials not yet conducted

Common Side Effects

  • Limited data - primarily preclinical research
  • Generally well-tolerated in animal studies

Stop Signs - Discontinue if:

  • Not applicable - not approved for human use

Contraindications

  • Not approved for human use
  • Experimental research peptide only
  • Cancers without membrane HDM-2 may not respond

Good Signs

  • White lyophilized powder
  • High purity (>95%)
  • Clear solution after reconstitution
  • Proper storage conditions

Warning Signs

  • Research chemical - limited quality standards
  • Not all cancers express membrane HDM-2

Bad Signs

  • Discoloration
  • Cloudy solution
  • Particulates visible
  • Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes
    PNAS (2010)

    PNC-27 binds membrane-bound HDM-2, inducing pore formation and cancer cell necrosis while sparing normal cells.

  • Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes
    PubMed (2024)

    PNC-27 also enters cancer cells and disrupts mitochondrial membranes.

  • PNC-27 Induces Tumor Cell Necrosis of Leukemia Cells
    Annals of Clinical & Laboratory Science (2014)

    PNC-27 induces necrosis of K-562 leukemia cells lacking p53 through p53-independent pathway.

  • PNC-27, a Chimeric p53-Penetratin Peptide
    PubMed (2022)

    PNC-27 binds HDM-2 in p53 peptide-like structure, induces selective membrane-pore formation leading to cancer cell lysis.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.