PNC-27 is a synthetic peptide that binds HDM-2, freeing tumor suppressor p53 and inducing selective cancer cell death through membrane disruption (membranolysis) while sparing healthy cells. It is being researched for ovarian, pancreatic, and breast cancers.
PNC-27
Also known as: HDM-2 Binding Peptide
Overview
Benefits
- Cancer cell targeting
- Tumor suppression
- Chemotherapy enhancement
Consider This Peptide If You Want To
- Support cellular apoptosis and regulation
- Aid cancer-targeted research or therapy synergy
Dosage & Administration
Dosage Guidelines
Recommended Dosage
• Amount:250 mcg
• Frequency:daily
• Duration:6 weeks
• Rest Period:8 weeks
• Time of Day:morning
• Ingestion:subcutaneous
Administration Routes:Subcutaneous
Research Findings on Dosage:
• Subcutaneous Injection:
◦ Commonly Reported Dosage:
▪ Low Dose: 100--500 mcg per day
▪ Moderate Dose: 500 mcg -- 2 mg per day
▪ High Dose: 2 mg -- 5 mg per day (used in more aggressive cases)
• Duration: Up to 8 weeks.
Important Notes:
• Use only under strict medical supervision.
• Some protocols use daily administration
• Others prefer 5 days on, 2 days off to prevent receptor downregulation.
• Subcutaneous (SQ) Injection -- Most common for systemic effects.
• Intravenous (IV) Infusion -- Used in aggressive protocols under supervision.
• Intratumoral Injection -- Directly into a tumor for localized treatment.
• Nebulization (Inhalation) -- Used experimentally for lung-related cancers
Mechanism of Action
Mechanism of Action
How this peptide works in the body
HDM-2 Binding:
PNC-27 mimics the p53-binding domain, competitively inhibiting HDM-2 (human double minute-2) from degrading p53. This allows p53 to accumulate and activate its tumor-suppressive functions, including upregulation of Bax and PUMA, leading to mitochondrial outer membrane permeabilization (MOMP) and activation of the caspase-9/caspase-3 apoptosis cascade, inducing programmed cancer cell death.
Selective Membranolysis:
PNC-27 selectively binds to HDM-2 overexpressed in cancer cell membranes, integrating into the lipid bilayer and forming transmembrane pores. These pores cause uncontrolled ion influx, osmotic imbalance, and rapid oncotic necrosis. Cancer cells undergo membrane rupture, triggering inflammatory responses and secondary immune clearance of tumor debris.
Non-Toxic to Normal Cells:
PNC-27 exhibits specificity for HDM-2-expressing cancer cells, avoiding toxicity in normal tissues with low HDM-2 levels. This selectivity is mediated by differential membrane composition, ensuring that healthy cells remain unaffected, even at high peptide concentrations. Studies confirm that PNC-27 does not compromise mitochondrial integrity or disrupt non-cancerous cell membranes.
Synergistic Effects:
PNC-27 enhances chemotherapy efficacy by increasing cancer cell susceptibility to paclitaxel, doxorubicin, and cisplatin. The combined action of membranolysis and intracellular apoptosis induction leads to a higher rate of tumor regression. PNC-27 also reduces chemotherapy resistance by preventing HDM-2-mediated p53 degradation, allowing for sustained apoptotic signaling.
Consider Stacking With
- Chemotherapy agents (e.g., paclitaxel)
Side Effects & Cautions
Common Side Effects
- Injection site redness, soreness, rash
- Nausea
- Edema
- Mild joint/muscle pain
Research & References
Research Highlights
Selective Toxicity:
Demonstrated ability to spare normal cells, including human hematopoietic stem cells, even at high doses.
In Vitro Efficacy:
Induced cell lysis in leukemia, melanoma, and pancreatic cancer models.
Chemo-Synergy:
Combined use with chemotherapy enhanced cytotoxic effects in ovarian cancer models.
References
Smith, S., & Michl, J. (2003). Development of PNC-27 as a selective anti-cancer peptide. Journal of Peptide Science
FDA Warning. (2017). Contamination risks associated with unregulated PNC-27 products
Michl, J., et al. (2005). Cytotoxic effects of PNC-27 in human cancer cell lines. Cancer Research
SUNY Downstate Research. (2010). Mechanisms of action of PNC-27 and PNC-28 in cancer therapy