PNC‑27 -Yuan peptide

PNC‑27

Product Description

PNC‑27 is a chimeric anticancer cell-penetrating peptide. Its core characteristic is the selective recognition of HDM‑2 on cancer cell membranes, rapid formation of membrane pores leading to cancer cell necrosis, with almost no damage to normal cells.

I. Basic Information

CAS Number: 1159861‑00‑3

Molecular Weight: Approximately 4.2 kDa

Structure: Composed of two fused segments:

N-terminus: Amino acids 12–26 of the p53 protein (HDM‑2 binding domain)

C-terminus: Transmembrane domain of penetratin

Sequence: PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG

II. Mechanism of Action (Core)

PNC‑27 targets membrane-bound HDM‑2 and rapidly kills cancer cells through a three-step process: "recognition‑pore formation‑cell lysis":

Targeted Binding

Membrane-bound HDM‑2 is highly expressed on cancer cell membranes, while barely present on normal cell membranes.

PNC‑27 specifically binds to membrane HDM‑2 via its N-terminal p53 domain and accumulates on cancer cell membranes within 15 minutes.

Conformational Change and Pore Formation

Upon binding, PNC‑27 forms an amphipathic α‑helix and oligomerizes to assemble into circular transmembrane pores (30–50 nm in diameter).

Rapid Cell Lysis (Necrosis)

The pores disrupt membrane integrity, allowing free permeation of ions and small molecules, leakage of intracellular contents, and osmotic imbalance.

Cells rapidly swell, rupture, and undergo necrosis within 30–180 minutes, independent of the caspase apoptotic pathway.

It remains effective against tumors with p53 mutations and apoptosis resistance.

III. Key Properties

High Selectivity: Only kills cancer cells expressing membrane HDM‑2, leaving normal cells unaffected.

Extremely Rapid Onset: Binding occurs within minutes and cell death within hours, differing from the slow action of conventional chemotherapy.

Broad Spectrum Activity: Effective in multiple tumor models including leukemia, breast cancer, melanoma, and pancreatic cancer.

Non-Genotoxicity: Does not directly damage DNA and is independent of the cell cycle.

IV. Current Research and Application Status

Stage: Used only for scientific research; not approved as a clinical drug.

Main Applications:

Research on hematologic malignancies such as acute myeloid leukemia (AML).

In vitro and animal model studies of solid tumors (e.g., breast cancer, pancreatic cancer).

Exploration of novel mechanisms underlying HDM‑2 membrane localization and tumor-targeted therapy.

Advantages: Promising for overcoming clinical challenges such as p53 mutations, multidrug resistance, and apoptosis resistance.

V. Differences from Conventional Anticancer Drugs

Characteristic	PNC‑27	Conventional Chemotherapy / Targeted Drugs
Target	Membrane HDM‑2 (unique to cancer cells)	Rapidly dividing cells / Intracellular kinases
Cell Death Mode	Necrosis (cell lysis)	Apoptosis / DNA damage
Selectivity	Extremely high (no harm to normal cells)	Low (bone marrow / gastrointestinal toxicity)
Onset Speed	Minutes‑hours	Days‑weeks
Drug Resistance	Rarely develops (membrane pore-forming mechanism)	Easily develops (mutation / efflux pump)

VI. Summary

PNC‑27 is an anticancer peptide with a unique mechanism and exceptional selectivity. It achieves precise killing of cancer cells by targeting membrane HDM‑2 and rapidly forming pores to induce lysis, providing new insights for overcoming drug resistance and improving safety. It is still in the basic and preclinical research stage, and remains far from clinical application.

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