Compounds / PNC-27
PNC-27
Also known as: PNC-27; p53-penetratin chimeric peptide; p53(12-26)-MRP; anti-cancer peptide PNC-27
Primary research focus: Oncology research (membrane HDM-2 targeting and tumor cell necrosis); laboratory use only
Last updated July 2026 · Reviewed against FDA labeling and published research.
What is PNC-27?
PNC-27 is a synthetic 32-amino-acid chimeric research peptide combining a p53-derived HDM-2-binding sequence (p53 residues 12 to 26) with a membrane-residency peptide from the Drosophila antennapedia homeodomain (penetratin). In laboratory models it binds HDM-2 expressed in cancer cell membranes and forms transmembrane pores, causing tumor cell necrosis while sparing normal cells. All evidence is preclinical: there are no human clinical trials, and it is not FDA-approved for any use.
The oncoprotein HDM-2 (the human homolog of MDM2), normally a nuclear regulator of p53, is also expressed in the plasma membranes of transformed cells but not normal cells, independent of p53 status. PNC-27's p53-derived segment binds the p53-binding pocket of membrane-resident HDM-2 (residues 1 to 109), while the peptide adopts an amphipathic helix-loop-helix conformation characteristic of pore-forming polypeptides and remains anchored in the bilayer. Immuno-scanning electron microscopy has imaged PNC-27 and HDM-2 in roughly 1:1 ratios in ring-shaped pore structures at the cancer cell surface. Pore formation causes extrusion of cell contents and necrosis (not apoptosis), and the effect is independent of p53 activity. Reported secondary activity includes binding to mitochondrial membranes causing mitochondrial disruption. Selectivity experiments support the mechanism: normal cells forced to express membrane-localized HDM-2 become susceptible, while cells expressing HDM-2 lacking the p53-binding domain do not.
How it’s supplied
Not an FDA-approved or commercially available medicine and not available in any clinical setting. It is sold as a research-grade lyophilized peptide for laboratory use. Research-grade products are not FDA-reviewed for identity, potency, or sterility.
Dosage Chart
Units shown are for a U-100 insulin syringe (100 units = 1 mL), calculated from the vial size and BAC water you select. Always confirm against your prescription and your syringe markings.
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Weeks 1-2 | 100mcg | 1x Daily | — |
| Weeks 3-4 | 200mcg | 1x Daily | — |
| Weeks 5-8 | 300mcg | 1x Daily | — |
| Weeks 9-12 | 400mcg | 1x Daily | — |
| Weeks 13-16 | 500mcg | 1x Daily | — |
- Rotate injection sites to reduce irritation and lipohypertrophy
- Not for use during pregnancy or breastfeeding
- Do not exceed the recommended dose to try to speed results
Potential Benefits and Side Effects
Effects reported in published research. Not a promise of results, and not medical advice.
- Reported in preclinical (cell culture and mouse xenograft) research only. No human benefit has been demonstrated and no therapeutic claim is supported.
- Selective necrosis of a range of cancer cell lines in vitro, including solid-tumor and leukemia lines, without effect on normal control cells.
- Activity independent of p53 status, including in p53-deleted cell lines.
- Direct imaging of transmembrane pore formation co-localized with membrane HDM-2.
- Utility as a laboratory tool for probing HDM-2 localization in tumor cell membranes.
- No human adverse-effect data exist.
- Preclinical reports describe an absence of effect on normal control cells, but this does not establish human safety.
- Pore-forming peptides carry inherent risk to normal tissue at sufficient exposure; systemic tolerability in people is entirely uncharacterized.
- Research-grade material carries identity and purity risks.
Warnings and contraindications
Important safety information. This is not exhaustive — read the full prescribing information and consult your prescriber or pharmacist.
- No FDA-approved labeling exists; the following reflect the compound's status and the limits of its evidence, not established label warnings.
- There are no human clinical trials of PNC-27. No safety, efficacy, dosing, or pharmacokinetic data exist in people, and no cancer treatment claim is supported.
- Cancer is a serious disease with established, evidence-based treatments. Substituting or delaying proven therapy in favor of an untested research peptide can be life-threatening, and anyone facing a cancer diagnosis should work with an oncologist.
- The selectivity for cancer cells is a cell-culture and animal-model finding; it has not been demonstrated in humans, and pore-forming peptides carry inherent risk to normal tissue at sufficient exposure.
- Much of the published mechanistic work comes from a single research group, and independent replication is limited.
- Research-grade material varies in identity and purity; safety in pregnancy and breastfeeding has not been studied.
- Not established; no FDA-approved labeling and no human use context. PNC-27 is a laboratory reagent, not a therapy.
Reconstitution Steps
How to prepare the lyophilized vial. Confirm specifics with your pharmacist or prescriber.
- Confirm the amount of peptide in the vial and the volume of diluent you intend to use before starting.
- Wash your hands and gather supplies: the lyophilized vial, the diluent (typically bacteriostatic water), an alcohol swab, and a sterile syringe.
- Let the vial and diluent reach room temperature if they were refrigerated or frozen.
- Wipe the rubber stopper of both the peptide vial and the diluent vial with a fresh alcohol swab and let them air dry.
- Draw the intended diluent volume into the syringe.
- Insert the needle into the vial and slowly release the diluent down the inside wall rather than directly onto the powder, to avoid foaming.
- Do not shake. Gently swirl or roll the vial until fully dissolved.
- Inspect the solution: it should be clear and colorless with no visible particles. Do not use if cloudy or containing particles.
- Note the resulting concentration (amount divided by diluent volume) so it matches the reconstitution calculator on this page.
- Label the vial with the reconstitution date and store as directed under reconstituted storage.
US regulatory status
Classifications are public record but can change. For reference only, not legal advice.
Development: PNC-27 arose from work by Matthew Pincus, Josef Michl, and colleagues (SUNY Downstate and collaborators) on peptides derived from the HDM-2-binding domain of p53 linked to a membrane-penetrating antennapedia sequence. The core finding, published in PNAS in 2010, is that PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding HDM-2 in their membranes rather than by restoring p53 signaling. Subsequent work extended the mechanism to non-solid tumors (a 2020 Anticancer Research study in K562 leukemia cells, which are p53-homozygously deleted), imaged the pores directly by immuno-scanning electron microscopy (2022), and described mitochondrial membrane disruption (2024). Despite a two-decade publication record and a coherent, well-imaged mechanism, PNC-27 has never entered human clinical trials: there is no registered trial, no IND, and no FDA approval. The evidence remains in vitro and in mouse xenograft models.
Notes: PNC-27 is not FDA-approved and has no recognized clinical use. It has no IND and no registered human clinical trial, and is sold only as a research chemical outside FDA quality oversight. It is not on the FDA 503A bulk drug substances list and is not eligible for 503A or 503B compounding. Marketing it as a cancer treatment would constitute an unapproved new drug claim. It is not a controlled substance.
International status
Pharmacokinetics
Storage and handling
Important Notes
Practical considerations for consistency and safety.
- PNC-27 has never been tested in humans. There are no clinical trials, no human safety data, and no established dose; it is a laboratory reagent.
- Cancer is a serious disease with proven treatments. Delaying or replacing evidence-based oncology care with an untested peptide is dangerous; discuss any interest with an oncologist.
- Its mechanism is unusual and well-imaged: it kills by forming pores after binding HDM-2 in the cancer cell membrane, causing necrosis, and works independently of p53 status.
- The cancer-selectivity finding comes from cell culture and animal models, not people.
- Most of the published work originates from a single research group; independent replication is limited.
Lifestyle Factors
- PNC-27 is a laboratory research reagent with no established human use context.
- Human lifestyle interactions are unstudied.
References
Related compounds
Important disclaimer
This page is an educational reference, not medical advice, a diagnosis, or a treatment recommendation, and not a substitute for your prescriber or pharmacist. Approval and regulatory status varies by compound and can change. Always confirm against current prescribing information and consult a qualified healthcare professional before making any decision about a medication.