PNC-27 Research, Specifications & Scientific Information

Introduction

PNC-27 rests on a claim that is unusual enough to be worth stating carefully before anything else. Not that a peptide can kill cancer cells — many can, and selectivity is the hard part — but that the selectivity comes from where its target protein sits.

HDM-2 is the human form of MDM2, a protein whose familiar role is nuclear: it binds p53 and marks it for degradation. The observation this compound is built on is different. HDM-2 was reported to be present in the plasma membranes of a variety of cancer cell lines and absent from the membranes of several untransformed lines ^[1]. A peptide carrying p53's HDM-2-binding domain would then have a target on the surface of cancer cells and nowhere on normal ones.

The strongest evidence for that account is not a correlation but an intervention: untransformed cells that were not susceptible were transfected to express HDM-2 at their surface, and became susceptible ^[1].

The evidence base also has a hard boundary. Every result is from cell culture or structural work, almost all of it from one collaboration, and no human study of this peptide exists. No animal study of PNC-27 itself was located for this page.

What Is PNC-27?

PNC-27 is a synthetic 32-residue chimeric peptide with two joined parts ^[2]:

• An HDM-2-binding domain corresponding to residues 12 to 26 of p53 — the segment of the tumour suppressor that contacts HDM-2 in the native interaction.
• A cell-penetrating leader sequence of the penetratin type, which carries the construct across or into membranes.

PubChem holds it under compound identifier 16201774 with CAS registry number 1159861-00-3, molecular formula C188H293N53O44S and average mass 4032 g/mol. No UNII code resolves for the substance.

It is not approved by the U.S. Food and Drug Administration for any indication, no marketing application for it is on record in the United States, and no clinical trial of it is registered anywhere.

PNC-27 Specifications

PubChem carries the peptide under compound identifier 16201774 with CAS registry number 1159861-00-3, molecular formula C188H293N53O44S and average mass 4032 g/mol. The primary literature describes it as a 32-residue chimera of two functional parts: an HDM-2-binding domain corresponding to residues 12 to 26 of p53, and a cell-penetrating leader sequence of the penetratin type. The residue string is not reproduced here in single-letter code because no public register queried for this page publishes it as a machine-readable sequence against those identifiers. No UNII code resolves for the substance. Conformational work reports that the p53-derived residues adopt, when bound to HDM-2, a structure superimposable on the corresponding residues of p53 itself, and that the leader sequence points away from the complex — so the two halves are structurally as well as functionally distinct.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does PNC-27 Work?

The reported mechanism is membranolysis — physical destruction of the cell membrane — rather than any signalling action, and that is a more unusual proposal than it first appears.

A peptide carrying p53's HDM-2-binding domain might be expected to work the way small-molecule MDM2 inhibitors do: entering the nucleus, displacing p53 from HDM-2, and allowing p53 to act. That is not what is described here. The account is that the peptide binds HDM-2 at the plasma membrane and, in doing so, forms pores that lyse the cell, producing necrosis rather than apoptosis ^{[1, 2]}.

The structural argument connecting the two halves of the molecule is specific. Conformational work reports that the p53-derived residues of the peptide, when bound to HDM-2, adopt a structure superimposable on the same residues of p53 bound to HDM-2 — so the peptide is engaging its target the way the parent protein does — while the leader sequence points away from the complex ^{[1, 2]}. On that model the binding domain anchors the peptide to membrane HDM-2 and the leader sequence lines the pore.

Selectivity, on this account, is not a property of the peptide at all. It is a property of the target's location, and the transfection experiment described in the next section is the test of that.

A later strand extends the mechanism to mitochondrial membranes as a second site of disruption ^[4], and the broader concept — peptide-induced transmembrane pore formation as a distinct mode of cell death — has been set out under the name poptosis ^[3].

PNC-27 Mechanism of Action

In vitro research

Where the target is. Significant levels of HDM-2 were reported in the membranes of a variety of cancer cell lines and not in the membranes of several untransformed cell lines. Colocalisation experiments reported the peptide binding to cell-membrane-bound HDM-2 ^[1].

The transfection test. Untransformed MCF-10-2A cells, not susceptible to the peptide, were transfected with a plasmid expressing full-length HDM-2 carrying a membrane-localisation signal. Cells expressing HDM-2 at their surface became susceptible ^[1]. This is the load-bearing experiment on this page: it converts a correlation between membrane HDM-2 and susceptibility into evidence of a causal relationship, and it is the kind of test most claims of this sort never undergo.

The pores, imaged. Immuno-scanning electron microscopy of treated cancer cells, using an anti-peptide antibody coupled to 6 nm gold and an anti-HDM-2 antibody coupled to 15 nm gold, reported the two labels in approximately 1:1 ratios within layered ring-shaped structures at pores near the cell surface. No pores formed in treated untransformed fibroblasts ^[2].

Cell-line range. Necrosis has been reported in leukaemia cells but not in normal haematopoietic cells ^[5], and in further epithelial and colonic lines, with susceptibility attributed throughout to membrane HDM-2 expression.

Intactness. One study addressed whether activity belongs to the whole molecule or to a fragment released from it, and reported lysis by the intact peptide ^[6].

Mitochondria. More recent work reports interaction with mitochondrial membranes causing mitochondrial disruption, as a second component of the mechanism ^[4].

Two limits apply throughout. Every result named here was obtained in cultured cells or in structural and computational systems. And the programme is largely a single collaboration; several of its authors declare inventorship on patents covering this peptide and its relative ^[2], which is disclosed in the papers and is relevant to how independently the findings have been scrutinised.

Findings in this section were obtained in cell culture and in structural and computational systems. Nothing in them establishes anything about intact animals or about humans.

What Is PNC-27 Being Researched For?

• Selective lysis of transformed cells — the central claim, examined across leukaemia, ovarian, colon and other cancer cell lines ^{[5, 1]}.
• The biology of membrane-associated HDM-2 — a finding that is of interest independently of any compound, since a nuclear regulatory protein appearing at the cell surface in transformed cells is a substantive observation ^[1].
• Peptide-induced pore formation as a mode of cell death — generalised under the name poptosis ^[3].
• Mitochondrial membrane disruption — a more recent extension of the mechanism ^[4].

None of that research is research into, or evidence about, research-grade material supplied for laboratory use, and none of it has been conducted in humans.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

PNC-27 vs Related Compounds

Against PNC-28

PNC-28 is the closely related chimera of the same p53-derived domain with a penetratin sequence, differing in arrangement. The distinction matters because the only in vivo work located for this family belongs to PNC-28: a 2006 study reporting that the peptide blocked pancreatic cancer cell growth in mice ^[7]. That is evidence about PNC-28. Attributing it to PNC-27 would be the exact error this library exists to avoid.

Against small-molecule MDM2 inhibitors

Nutlins and their successors block the p53-HDM-2 interaction in the nucleus to restore p53 activity, and several have entered clinical trials. This peptide is proposed to act at the membrane and to lyse the cell outright ^[1]. Despite sharing a named target, the two approaches have almost nothing else in common.

Against FOXO4-DRI

FOXO4-DRI is the other designed protein-interaction peptide in this library, also built around a p53 interaction. It disrupts FOXO4-p53 binding to trigger apoptosis in senescent cells; this one is proposed to disrupt a membrane. Both are structure-led designs; their mechanisms are unrelated.

Against the host-defence peptides

LL-37 also forms membrane pores, but does so through amphipathic interaction with lipid bilayers rather than through binding a specific protein. The distinction is the whole of this compound's selectivity claim.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

PNC-27 is a 32-residue chimeric peptide of molecular formula C188H293N53O44S and average mass 4032 g/mol, under PubChem compound identifier 16201774 and CAS registry number 1159861-00-3.

Two domains, and both are required. The p53-derived segment provides target binding and the penetratin-type leader provides membrane interaction, and the structural model places them in distinct positions relative to the bound complex ^[2]. A truncated construct retaining only one is a different molecule with a different expected behaviour, which is also why the closely related PNC-28 is a separate substance rather than a variant spelling.

No published sequence in a public register. PubChem gives formula and mass but no single-letter residue string, and no UNII resolves. The specification table therefore describes the sequence rather than stating it. For a 32-residue peptide that is a material gap, because sequence is what makes independent identity confirmation possible.

Strongly cationic, by design. Penetratin-type leaders are arginine- and lysine-rich, and that charge is what drives their interaction with membranes. A peptide of this size and charge adsorbs appreciably to glass and to some plastics from dilute aqueous solution, so nominal and actual concentrations diverge in dilute preparations unless handled for it.

Length brings the synthesis burden. At 32 residues, deletion sequences missing a single residue are the characteristic impurity of solid-phase synthesis. They differ from the target by roughly 3% of its mass, co-elute closely, and require a method designed to resolve them.

Salt form. Peptides of this charge are ordinarily isolated as trifluoroacetate salts, which contribute substantially to measured mass. A purity or mass figure that does not state the counter-ion and the water content is incomplete.

Frequently Asked Questions

Scientific References

1. Sarafraz-Yazdi E, Bowne WB, Adler V, et al.. Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes Proceedings of the National Academy of Sciences of the United States of America; 2010. PMID 20080680 doi:10.1073/pnas.0909364107
2. Sarafraz-Yazdi E, Mumin S, Cheung D, et al.. PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis Biomedicines; 2022. PMID 35625682 doi:10.3390/biomedicines10050945
3. Pincus MR, Silberstein M, Zohar N, et al.. Poptosis or Peptide-Induced Transmembrane Pore Formation: A Novel Way to Kill Cancer Cells without Affecting Normal Cells Biomedicines; 2024. PMID 38927351 doi:10.3390/biomedicines12061144
4. Krzesaj P, Adler V, Feinman RD, et al.. Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes Causing Mitochondrial Disruption Annals of clinical and laboratory science; 2024. PMID 38802154
5. Thadi A, Lewis L, Goldstein E, et al.. Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells Anticancer research; 2020. PMID 32878773 doi:10.21873/anticanres.14488
6. Sookraj KA, Bowne WB, Adler V, et al.. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide Cancer chemotherapy and pharmacology; 2010. PMID 20182728 doi:10.1007/s00280-009-1166-7
7. Michl J, Scharf B, Schmidt A, et al.. PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo International journal of cancer; 2006. PMID 16688716 doi:10.1002/ijc.22029

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.