PNC 27

PNC-27 is a peptide of 32 amino acids that joins two functions in one molecule: one segment comes from the tumor suppressor p53, the other is a membrane-binding domain that anchors the peptide to cell surfaces. It was designed by groups at the State University of New York who were looking for a way to attack tumor cells through their membrane rather than through their metabolism.

The mechanism hinges on a single protein. HDM-2 (Human Double Minute 2) is present in markedly elevated amounts in many cancer cell types but only sparsely in healthy cells. PNC-27 binds HDM-2 in a p53-like conformation, forms pores in the membrane and thereby triggers necrosis of the cell. Cells with low HDM-2 levels remain intact in the experiments. This has been described for cell lines from pancreas, breast and leukemias.

What else is known:

• The intact peptide itself is active, not merely a breakdown product.
• In a mouse model of ovarian cancer, toxicity was examined after dosing into the abdominal cavity.
• Tumor cells that had survived paclitaxel treatment responded more sensitively to PNC-27 in cell experiments.
• The unmodified form has a half-life of only about half an hour.

The classification is unambiguous: this is basic oncology research. Development for use in humans never took place, and clinical trials do not exist. Studies dose parenterally; outside the oncology laboratory the peptide is not established.

There is no human safety profile for PNC-27 because it was never developed for that purpose. Everything below comes from the preclinical literature and says nothing about tolerability in humans.

• Mode of action: The peptide destroys the membranes of HDM-2-rich cells and drives them into necrosis. That healthy cells are spared has been shown in cell models but never verified in humans.
• No human data: Clinical safety studies do not exist. Nothing about tolerability, doses or side effects can be derived from the literature.
• Injection site: With parenteral dosing a local irritation is to be assumed; this, too, was never recorded systematically.
• Narrow frame: Beyond basic oncology research, any use lacks any data basis whatsoever.

This summary is no substitute for medical advice.

• The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide - shows that the unaltered peptide itself triggers lysis of the tumor cells.
• Evaluation of PNC-27-mediated toxicity in an intraperitoneal mouse model of human ovarian cancer - examines toxicity in a mouse model of ovarian cancer after intraperitoneal dosing.
• Tumor cells surviving the cytotoxic effect of paclitaxel are sensitized to anti-cancer peptide PNC-27 - reports that tumor cells surviving paclitaxel respond more sensitively to the peptide.