PNC-27

What PNC-27 is

PNC-27 is an artificial peptide made of two parts. One corresponds to amino acids 12 to 26 of the tumor suppressor p53, that is, the segment with which p53 binds to the protein HDM-2. The other is penetratin, a sequence that carries peptides across cell membranes. A shorter variant with amino acids 17 to 26 is called PNC-28.

It was developed by the research group around Pincus and Michl at the Downstate Medical Center of the State University of New York; the first paper appeared in 2001. To this day, almost all publications come from this group, most recently its own review from 2024.

What is rated is the state of knowledge. For PNC-27, it ends in the laboratory and in animal experiments.

How it works

According to the developer group’s work, many cancer cells carry HDM-2 not only inside the cell but also in their outer membrane, healthy cells hardly at all. PNC-27 binds to HDM-2 there, the complexes assemble into channels, the membrane becomes permeable, and the cell leaks out. The group calls this “poptosis”; biologically it is necrosis, not programmed cell death.

The group tested this link directly in 2010: normal cells that PNC-27 could not harm became vulnerable as soon as HDM-2 was inserted into their membrane in the laboratory (Sarafraz-Yazdi 2010). Because the attack starts at the membrane, PNC-27 also worked in cell culture against cancer cells without functioning p53.

What the studies show

Kanovsky 2001: the origin

Three peptides from the HDM-2-binding region of p53, each coupled to penetratin, were toxic to human cancer cells in cell culture, while a control peptide with the same transport sequence was not (Proc Natl Acad Sci USA). Normal cells, including stem cells from umbilical cord blood, continued to grow unimpaired. Cancer cells without p53 died just like those with intact or altered p53.

Michl 2006: PNC-28 in nude mice

The shorter variant PNC-28 was given for two weeks into the abdominal cavity of nude mice that were simultaneously implanted with tumor cells from a rat pancreatic cancer line (Int J Cancer). There, the tumors were completely destroyed. At a distant site, PNC-28 blocked tumor growth during administration; afterwards the tumors grew back weakly. Tumors that had already grown initially shrank and then grew more slowly than under a control peptide. The authors saw the best chances with direct administration at the tumor.

Wang 2020: leukemia in a mouse model

A group at City of Hope, not identical with the developers, found membrane-bound HDM2 on acute myeloid leukemia cells, including leukemic stem cells, but not on healthy blood stem cells (Leukemia). In transplantation experiments with human and mouse leukemia, PNC-27 killed both the bulk of the leukemia cells and the leukemic stem cells and spared healthy blood stem cells. The pathway was described somewhat differently here: PNC-27 strengthened the binding of HDM2 to E-cadherin, whose breakdown damaged the membrane.

Sarafraz-Yazdi 2015: tumor cells from patients in the laboratory

Cells were obtained from the tumors of two patients with newly diagnosed ovarian cancer and treated with PNC-27 in the laboratory (Ann Clin Lab Sci). It inhibited their growth in a dose-dependent manner, including in chemotherapy-resistant cell lines; a control peptide did not. This is a laboratory experiment on human cells, not a treatment of humans.

Where the data stop

• Nothing in humans. There is no study on efficacy, none on tolerability and none on how long PNC-27 stays in the body and where it ends up. No trial is registered in the ClinicalTrials.gov registry.
• The route to the tumor. In the mouse experiment, PNC-28 worked best when it was given where the tumors were located. Whether a peptide reaches a tumor in the human body in sufficient amounts and intact has not been tested.
• Who collected the data. Apart from the 2020 leukemia paper, the findings come from the developer group, including the 2024 review. Independent confirmation in solid tumors is lacking.
• Cell culture is not a patient. That cancer cells die in the dish holds true for a great many substances. Most never achieve an effect in humans.

Status, approval and legal

PNC-27 is not approved as a medicine anywhere, neither in Germany nor in the EU or the US, and no trial is registered in the ClinicalTrials.gov registry.

In January 2017, a laboratory of the US Food and Drug Administration (FDA) found the bacterium Variovorax paradoxus in a sample of PNC-27 that was advertised as a treatment or cure for cancer. The FDA lists the case as an example of illegally marketed, unapproved cancer products.

In Germany, advertising for medicines outside professional circles may not refer to the detection, prevention, elimination or alleviation of malignant neoplasms (§ 12 of the German Medicines Advertising Act (Heilmittelwerbegesetz) with Annex A No. 2). We do not give dosage information for unapproved substances.

Safety

There are no safety data in humans. In the mouse experiments, the authors reported no damage to healthy tissues and blood stem cells; this cannot be transferred to humans.

What is concretely documented is a product risk: the bacterial contamination that the FDA found in a sample in 2017 and cites as an example of a direct health risk. The FDA also points out that such products cause indirect harm when they delay or interfere with proven treatments. If you or someone close to you with cancer is considering PNC-27, the conversation belongs first with the treating oncology team.

Sources

• Kanovsky M et al., Proc Natl Acad Sci USA 2001 – p53 peptides with penetratin, selectively toxic to cancer cells (cell culture)
• Sarafraz-Yazdi E et al., Proc Natl Acad Sci USA 2010 – PNC-27 binds HDM-2 in the membrane of cancer cells
• Michl J et al., Int J Cancer 2006 – PNC-28 slows pancreatic tumors in nude mice
• Wang H et al., Leukemia 2020 – membrane-bound HDM2 as a target in acute myeloid leukemia (mouse)
• Sarafraz-Yazdi E et al., Ann Clin Lab Sci 2015 – PNC-27 on freshly obtained ovarian cancer cells in the laboratory
• Pincus MR et al., Biomedicines 2024 – review by the developer group on pore formation
• FDA, questions and answers on illegally marketed cancer products – bacteria found in PNC-27 (January 2017)
• German Medicines Advertising Act (Heilmittelwerbegesetz), annex to § 12 – no advertising to the public for medicines for malignant neoplasms
• ClinicalTrials.gov – search for PNC-27, no registered trial