EmergingLongevity

PNC-27

PNC27

Anti-Cancer Peptide | p53-HDM-2 Disruptor

Half-life

Less than 24 hours (requires daily dosing in studies)

Chain length

32 amino acids

Reference frequency

Research protocols vary by study

Research overview

DoseGear research brief

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.

Compound background

Development & research timeline

Study windows describe what researchers measured, not when an individual should expect a result.

Origin & development

Engineered p53-derived peptide linked to a membrane-penetrating segment.

What it is researched for

Experimental cancer-cell killing through proposed HDM2 interaction and membrane disruption.

Research observation window

No validated clinical tumor-response timeline is reported.

Reference data

Lyophilized vial injectable protocols

Not personalized dosing instructions

Only injectable vial references are shown. Nasal, topical, and unsupported non-vial schedules are excluded.

Research context	Amount	Frequency	Route
Research protocol	Variable by study	Research protocols	IP or direct tumor injection (research)

Reference cycle

Not established - no human clinical trials

Reference storage

Refrigerate at 2-8°C

Safety context

Reported side effects

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

Contraindications & cautions

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

Scientific references

01
Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes
Scientific citationAnticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes. PNAS (2010).
02
Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes
Scientific citationAnti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes. PubMed (2024).
03
PNC-27 Induces Tumor Cell Necrosis of Leukemia Cells
Scientific citationPNC-27 Induces Tumor Cell Necrosis of Leukemia Cells. Annals of Clinical & Laboratory Science (2014).
04
PNC-27, a Chimeric p53-Penetratin Peptide
Scientific citationPNC-27, a Chimeric p53-Penetratin Peptide. PubMed (2022).

This DoseGear profile combines published scientific literature with lyophilized-vial protocol references. Citations are provided for independent review.

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