IMMUNEResearch OnlyANTI-CANCERP53MDM-2

PNC-27

Also known as: PNC27 · p53 C-terminal peptide · MDM-2 targeting peptide

27 views/week 134 citations 0 edits Updated 6/8/2026

PNC-27 is a synthetic anticancer peptide derived from the MDM-2-binding domain of p53, fused to a membrane-penetrating sequence. It selectively induces membranolytic cell death in cancer cells that overexpress HDM-2 while leaving normal cells unharmed.

STRUCTURE

Molecular Composition

FORMULA

C₁₅₄H₂₅₉N₄₅O₄₃S₂

MOL. WEIGHT

3,369.1 Da

CAS NUMBER

N/A

TARGET

Surface HDM-2

SEQUENCE

32 amino acids

MECHANISM

Membranolysis

AMINO ACID CHAIN VISUALIZATION

Pro-p53 domain

p53 MDM-2 binding core

—

NH-CO

His-p53

MDM-2 contact residue

—

NH-CO

Leader sequence

Membrane penetration

—

NH-CO

Arg-penetratin

Cell membrane anchoring

—

NH-CO

MDM-2 mimic

Surface HDM-2 binding

—

NH-CO

Phe-pore

Membranolytic pore core

SEQUENCEP-H-L-R-M-F

MECHANISMS

How It Works

🎯

Cancer-Selective Surface HDM-2 Binding

PNC-27 targets HDM-2 (human MDM-2) protein aberrantly displayed on the outer surface of cancer cell membranes. Normal cells do not express HDM-2 extracellularly, making this targeting mechanism highly tumour-selective. PNC-27's p53-derived domain binds surface HDM-2 with high affinity, initiating oligomerisation.

💥

Membranolytic Pore Formation

HDM-2/PNC-27 complexes in the cancer cell membrane oligomerise to form transmembrane pores. These pores disrupt osmotic balance and membrane integrity, causing rapid membranolytic necrosis within hours of exposure. This physical destruction mechanism is fundamentally different from apoptosis.

🔬

p53-Independent Activity

Because PNC-27 kills via membrane lysis rather than p53-mediated apoptosis pathways, it is effective against cancers with p53 mutations — which account for over 50% of all human tumours and are a major source of chemotherapy resistance. Activity in p53-null cell lines has been confirmed.

🛡️

Resistance Mechanism Independence

Multi-drug resistance mechanisms (P-glycoprotein efflux pumps, anti-apoptotic Bcl-2 overexpression, altered pro-caspase levels) do not protect against PNC-27's membranolytic mechanism. Cells resistant to doxorubicin, paclitaxel, and other chemotherapeutics remain sensitive to PNC-27 in preclinical models.

OVERVIEW

Research Overview

PNC-27 is a 32-amino acid chimeric peptide developed by Dr. Matthew Pincus at SUNY Downstate. Cancer cells overexpressing HDM-2 display this protein on their cell surface — PNC-27 binds to surface HDM-2, triggering pore formation and membranolytic necrosis specifically in tumour cells. Crucially, normal cells do not express HDM-2 on their surface, making PNC-27 highly cancer-selective.

Mechanism of Action

PNC-27 binds to HDM-2 protein displayed on the outer surface of cancer cell membranes. This interaction initiates oligomerisation of HDM-2 and PNC-27 complexes within the lipid bilayer, forming transmembrane pores that cause rapid osmotic lysis of cancer cells. The mechanism is independent of intracellular p53 signalling and is therefore effective in p53-mutant cancers.

DOSAGE

Dosage & Administration

RESEARCH (IN VITRO / XENOGRAFT)

DOSE

Variable (10–100 μM in vitro; mg/kg range in vivo)

FREQUENCY

Per study protocol

NOTES

No established human dosing. In vitro studies use 10–100 μM concentrations. Animal xenograft studies use mg/kg IV or IP dosing. Human clinical protocol does not yet exist.

PNC-27 is a preclinical oncology research compound only. No human clinical trials have been completed. Mechanism of action is unique and compelling, but in vivo pharmacokinetics, stability, and tolerability in humans have not been established. Researchers should follow institutional biosafety protocols for novel peptide cancer research agents.

CYCLING

Cycle Duration Guide

ON CYCLE

Per preclinical study protocol

OFF CYCLE

N/A

No human cycling data exists. Preclinical xenograft studies use variable dosing windows. This remains early-stage oncology research.

⚠

Research-only compound. No human clinical trials completed. Membranolytic mechanism could theoretically affect any cell expressing surface HDM-2 under pathological conditions. Handle with appropriate research-grade precautions.

View full Cycle Guide →

NOTES

Research Notes

Research compound only — no human clinical trials completed. Mechanism is unique (membranolysis rather than apoptosis) and resistant to common drug resistance pathways. Active research in pancreatic, breast, and melanoma models. No established human dosing protocol.

◆Quick Reference

FORMULAC₁₅₄H₂₅₉N₄₅O₄₃S₂

MOL. WEIGHT3,369.1 Da

LENGTH32 amino acids

ORIGINSynthetic chimeric peptide; developed by Matthew Pincus, SUNY Downstate

HALF-LIFEUnknown; likely short (minutes) in vivo

SOLUBILITYSoluble in DMSO then diluted in PBS; limited aqueous solubility

STATUSResearch Only

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