PNC-27
Anti-Cancer Peptide · p53-HDM-2 Disruptor
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.
Overview
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.
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.
Research indications
What the compound has been studied for, grouped by body system. Effect size is the reported magnitude where it was measured — not a recommendation.
PNC-27 shows selective cytotoxicity against pancreatic cancer cells in research.
Demonstrated effectiveness against breast cancer cell lines.
Induces necrosis of K-562 leukemia cells through HDM-2 binding.
Shows selective targeting of melanoma cells.
Most effective against cancers with high membrane HDM-2 expression.
Model compound for studying cancer-selective therapies.
A large effect in a weak study and a small effect in a strong one are different things. Effect size is never evidence of use in people.
- Class
- Chimeric peptide
- Molecular weight
- 3500 Da
- Half-life
- ~12 h
- Typical dose
- Not established - preclinical research only
- Frequency
- Research protocols vary by study
- Cycle length
- Not established - no human clinical trials
- Storage
- Refrigerate at 2-8°C
Molecular data
- Type
- Chimeric peptide
- Molecular weight
- 3500 Da
- Half-life
- 720 min
Dosing reference
Doses reported in the literature and by suppliers. These are a record of what has been used in research — reference, never instruction.
| Context | Route | Amount | Frequency |
|---|---|---|---|
| Research protocol | IP or direct tumor injection (research) | Variable by study | Research protocols |
Interactions
Potential for combination therapy being researched.
Combination studies not yet published.
Quality checklist
- ✓White lyophilized powder
- ✓High purity (>95%)
- ✓Clear solution after reconstitution
- ✓Proper storage conditions
- !Research chemical - limited quality standards
- !Not all cancers express membrane HDM-2
- ×Discoloration
- ×Cloudy solution
- ×Particulates visible
What to expect
Safety
- Limited data - primarily preclinical research
- Generally well-tolerated in animal studies
- Not applicable - not approved for human use
- Not approved for human use
- Experimental research peptide only
- Cancers without membrane HDM-2 may not respond
FAQ
Why is PNC-27 described as 'cancer cell-selective' when normal cells can express HDM-2?
The key difference is location. Normal cells express HDM-2 intracellularly, not on their cell surface. PNC-27 requires membrane-bound HDM-2 to form pores. Cancer cells uniquely express HDM-2 on their plasma membrane, making them susceptible to attack while normal cells are completely spared. This surface expression is a cancer-specific vulnerability.
Is PNC-27 closer to clinical trials than other peptide cancer therapies?
Not yet. PNC-27 remains in preclinical research with no human clinical trials initiated as of 2025. While it's been studied since 2000, it hasn't progressed to human testing. That's partly because cancer drug development is slow and partly because peptide therapeutics face delivery challenges that are being actively researched.
Why would someone take PNC-27 if it doesn't prevent cancer recurrence?
PNC-27 is purely experimental—it eradicates tumor cells in mouse models through a unique mechanism (membrane pore formation + mitochondrial damage). Once human trials exist (which they don't yet), the intent would be cancer treatment, not prevention. Until then, it's a research tool for understanding cancer-selective therapies.
Could PNC-27 work on cancers that don't express HDM-2?
No. PNC-27's entire mechanism depends on membrane HDM-2 binding. Cancers without membrane HDM-2 expression wouldn't respond. This is both a strength (high selectivity) and a limitation (requires the right cancer type). Assessing HDM-2 status would be critical before attempting any therapeutic use.