PNC 27

Technical data

CAS

1159861-00-3

Molecular formula

C188H293N53O44S

Molecular weight

4031.8 g/mol

Identity and composition

PNC-27 is a 32-residue chimeric research peptide derived from the region of the suppressor protein p53 that binds to HDM-2 (human MDM2). It is studied in preclinical models for its selective interaction with HDM-2 located in the membrane of various tumor cells. It is a material for experimental use, not an approved drug.

As for its chemical identity, its sequence is confirmed in the peer-reviewed literature: PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG (H-Pro-Pro-Leu-Ser-Gln-Glu-Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu-Lys-Lys-Trp-Lys-Met-Arg-Arg-Asn-Gln-Phe-Trp-Val-Lys-Val-Gln-Arg-Gly-OH). Residues 1-20 correspond to the region of p53 (aa 12-26) that binds to HDM-2, whereas the C-terminal segment is a membrane-residence/penetration peptide (MRP).

No confirmed CAS number, molecular weight or molecular formula is available in an authorized database (PubChem/DrugBank); the values that circulate come only from supplier catalogs, so they are not reported here. It is offered in presentations of 5 mg y 10 mg.

Product for research use.

Mechanism of action

PNC-27 is a chimeric peptide that fuses the subregion of p53 that binds HDM-2 (residues 12-26) with a membrane-residence/penetration peptide (MRP). In the preclinical studies reviewed, the peptide co-localizes with HDM-2 that is aberrantly expressed on the plasma membrane of a broad spectrum of cancer cells, but not on normal cells (PNAS 2010; PMC2836618).

Upon binding to membrane HDM-2, the p53 subregion adopts the crystallographic HDM-2-binding conformation and the peptide would induce the formation of transmembrane pores, which has been described as membranolysis and p53-independent necrosis, rather than apoptosis. In the in vitro models, cell death depended on the expression of HDM-2 in the membrane: transfecting HDM-2 with a membrane-localization signal into resistant non-transformed cells (MCF-10-2A) rendered them susceptible, and deletion of intracellular p53 did not prevent the effect (Ann Clin Lab Sci 2014; PMID 25117093). Disruption of mitochondrial membranes has also been reported.

Pharmacokinetics

No pharmacokinetic parameters (half-life, clearance, bioavailability) were identified in the primary sources reviewed. The action described in the literature is mediated at the membrane surface and independent of internalization or intracellular processing, but no quantitative pharmacokinetic data are reported. Any PK characterization should be considered pending within the exclusively experimental context of this material.

Scientific evidence

All the evidence identified is preclinical and of a preliminary nature: these are in vitro and ex vivo works. In cancer cell lines (for example, K562 leukemia), selective necrosis dependent on membrane HDM-2 has been observed, with preservation of normal lymphocytes (PMID 25117093). In primary cells derived from patients with epithelial ovarian cancer, including chemoresistant lines, a dose-dependent ex vivo cytotoxicity has been investigated, with specificity confirmed by the inactive control peptide PNC-29 (PMID 26663795).

No clinical trial registered in ClinicalTrials.gov for PNC-27 was located. Claims of completed clinical trials or of clinical use appear only in secondary sources and could not be substantiated in the primary literature nor in a trials registry. The indications explored experimentally (leukemia and ovarian cancer) are presented by the authors as potential, not as established.

Research applications

Ideal for (research):

• In vitro and ex vivo studies on the interaction of p53-derived peptides with membrane-localized HDM-2/MDM2.
• Research on p53-independent necrosis mechanisms and transmembrane pore formation in tumor cell lines.
• Comparative sequence-specificity assays against control peptides (for example, PNC-29).
• Bench work in experimental oncology and membrane biology.

Not applicable for:

• clinical use, therapeutic use, diagnosis or any clinical application.
• Veterinary use or in food.
• Extrapolation of preclinical results to efficacy or safety in people.

Product for research use.

Research protocols

In the ex vivo studies with primary ovarian cancer cells, a cytotoxicity is described dose-dependent, but the primary sources reviewed do not report a numerical concentration scheme that can be cited here in a verifiable manner (PMID 26663795). For this reason, no doses in mg or molar concentrations are specified.

As a general laboratory guideline, the working conditions (concentration, vehicle, exposure time, and cell type) must be defined by the investigator and validated against appropriate controls, including an inactive control peptide such as PNC-29 to verify sequence specificity. Any quantitative protocol must be based on the corresponding primary source and on the laboratory's own optimization.

Reconstitution

As standard laboratory practice, lyophilized peptides are usually reconstituted with bacteriostatic water (sterile water with approximately 0.9% benzyl alcohol) or with sterile water for injection, depending on the experimental design.

General guide:

• Let the vial reach room temperature before opening it.
• Add the diluent, letting it run slowly down the wall of the vial, without injecting it directly onto the powder.
• Do not shake; gently swirl the vial until fully dissolved.
• Calculate the diluent volume according to the desired working concentration for the 5 mg or 10 mg presentations.

This is general handling guidance; it does not constitute instructions for human use.

Stability and storage

As a laboratory handling standard for peptides:

• Lyophilized: it is advisable to store it cold, typically refrigerated and, for prolonged storage, frozen, protected from moisture and light. In their dry form, peptides are usually more stable.
• Reconstituted: once in solution, it is handled refrigerated for short-term use and frozen (ideally in aliquots) for longer periods, minimizing freeze-thaw cycles that can degrade the peptide.

These are general storage recommendations; the specific optimal conditions must be verified in the laboratory.

Safety profile

The documented safety evidence is limited to in vitro/ex vivo selectivity. Under the conditions tested, PNC-27 induced necrosis of tumor cells whereas normal lymphocytes, hematopoietic cells and non-transformed lines (for example, MCF-10-2A) were not affected as reported (PMID 25117093). The control peptide PNC-29 showed no effect, which supports sequence specificity.

No safety, toxicology, or adverse-event data in humans were identified. As this is exclusively research material, it should be handled with standard laboratory precautions (personal protective equipment, good practices), and there is no profile of clinical contraindications because it is not intended for use in people.

Comparative context

PNC-27 belongs to a family of p53-derived peptides. It is closely related to PNC-28, which shares the same active concept derived from p53, and with PNC-29, the inactive control peptide used to confirm sequence specificity.

Its distinctive feature compared with classic MDM2/HDM-2 antagonists (for example, the nutlins) is the mechanism: the nutlins act by restoring the intracellular signaling of p53, whereas PNC-27, according to the preclinical literature, does not depend on that pathway. Instead, it exploits HDM-2 located on the membrane of the cancer cell to form lytic pores, which makes its described activity independent of intracellular p53.

History and development

PNC-27 was developed and characterized in the academic literature as a chimeric peptide that combines the region of p53 (aa 12-26) that binds to HDM-2 with a membrane residency/penetration peptide (MRP). The complete 32-residue sequence and the HDM-2-binding conformation were described in a peer-reviewed report published in PNAS in 2010 (PMC2836618). Subsequent work explored its membrane HDM-2-dependent activity in leukemia cell lines (Ann Clin Lab Sci 2014; PMID 25117093) and its ex vivo cytotoxicity in patient-derived ovarian cancer cells (2015; PMID 26663795). All documented development remains in the preclinical phase.

FAQ

Scientific references (8)

Peer-reviewed literature on PNC 27, with its PubMed identifier when available:

• Anticancer Peptide PNC-27 Adopts an HDM-2-Binding Conformation and Kills Cancer Cells by Binding to HDM-2 in Their Membranes (Sarafraz-Yazdi, et al. · Proceedings of the National Academy of Sciences (PNAS) · 2010) PMID 20080680.
• The Anti-Cancer Peptide, PNC-27, Induces Tumor Cell Necrosis of a Poorly Differentiated Non-Solid Tissue Human Leukemia Cell Line That Depends on Expression of HDM-2 in the Plasma Membrane of These Cells (Davitt, et al. · Annals of Clinical and Laboratory Science · 2014) PMID 25117093.
• 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 (Sarafraz-Yazdi, et al. · Biomedicines · 2022) PMID 35625682.
• Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes Causing Mitochondrial Disruption (Krzesaj, et al. · Annals of Clinical and Laboratory Science · 2024) PMID 38802154.
• Poptosis or Peptide-Induced Transmembrane Pore Formation: A Novel Way to Kill Cancer Cells without Affecting Normal Cells. (Pincus MR, et al. · Biomedicines · 2024) PMID 38927351.
• HDM-2-Targeting Peptide PNC-27 Kills Cervical Cancer Cells but not Normal Cervical Cells. (Krzesaj PK, et al. · Ann Clin Lab Sci · 2025) PMID 40750238.
• Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Colonic Epithelial-derived Progenitor Cells. (Thadi A, et al. · Anticancer Res · 2021) PMID 33419797.
• PNC27 anticancer peptide as targeting ligand significantly improved antitumor efficacy of Doxil in HDM2-expressing cells. (Darban SA, et al. · Nanomedicine (Lond) · 2017) PMID 28565974.

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