PNC-28
Shorter PNC-27 analog · p53-derived HDM-2 binder that opens pores in cancer-cell membranes
PNC-28 is a shorter version of PNC-27, a fragment of the tumor-suppressor p53 on a membrane-anchoring leader. It binds HDM-2, a protein on cancer-cell surfaces, and opens pores that rupture them, sparing normal cells. In mice it destroyed pancreatic tumors in about two weeks.
The short version
A protein called HDM-2 sits on the outer membrane of cancer cells but not normal ones. PNC-28 grabs it, tears holes in the membrane, and the cell bursts. Normal cells are left alone.
The standout result is in a living animal. In mice with pancreatic tumors, injections over about two weeks destroyed the tumors and spared healthy tissue.
How it works
Two halves, one job. PNC-28 is a 27-amino-acid peptide built from two pieces. Residues 17 to 26 of human p53 (ETFSDLWKLL) join the same 17-residue Antennapedia leader as PNC-27 (KKWKMRRNQFWVKVQRG). It is PNC-27 minus its first five p53 residues (PPLSQ, p53 12 to 16).
Docks on the cancer membrane. Cancer cells carry HDM-2 (MDM2) in their outer membrane. Normal cells do not. PNC-28 binds it, forms transmembrane pores, and the cell dies by necrosis, spilling its contents.
The leader sets the death mode. In a 2008 study on pancreatic cancer cells, the p53 fragment alone drove apoptosis, the cell's orderly shutdown. With the leader attached it switched to membrane-pore necrosis, and labeled peptide sat on cancer-cell membranes, not normal ones.
Side effects and what to watch
What people notice. Nothing is on record. The studies ran in cell culture and in mice.
Contamination has been found in its sibling. In 2017 the U.S. Food and Drug Administration warned the public not to use PNC-27 after sold samples tested positive for two bacteria, Variovorax paradoxus and Ralstonia insidiosa.
A death has been reported with PNC-27. A case report describes a fatal gastrointestinal hemorrhage during PNC-27 use. No PNC-28 case is published.
Take care with sterility. PNC-28 is the same class sold through the same channels, so contamination, infection and immune reactions are the risks to watch.
Common questions
What has the research found?
In cell culture, pancreatic cancer cells died by necrosis through membrane pores while normal cells were spared. In nude mice carrying pancreatic tumors, injections into the abdominal cavity over about two weeks destroyed the tumors and spared normal cells.
How does PNC-28 tell cancer cells from normal ones?
It reads the membrane. Cancer cells carry HDM-2 on their outer membrane and normal cells do not. The p53 fragment binds that surface HDM-2, so only cells displaying it get pores.
Why does it kill by rupture rather than apoptosis?
The membrane leader. On its own the p53 fragment drives apoptosis, the cell's orderly shutdown. Anchored in the membrane, the peptide forms pores instead and the cell dies by necrosis. A scrambled p53 version with the leader does nothing.
How is PNC-28 different from PNC-27?
Both carry the same membrane-anchoring leader. PNC-27 holds p53 residues 12 to 26. PNC-28 holds 17 to 26, the same stretch minus its first five residues. Both work the same way, and the mouse tumor result belongs to PNC-28.
How is it dosed?
The only amounts on record are research doses given to mice into the abdominal cavity over about two weeks. Mouse amounts do not convert to a person, so this page gives the research record rather than a schedule.
Deep dive
Doses used in studies · Molecular identity · References
04From the researchDoses used in studies
These are the studies behind PNC-28, run in cell culture and in nude mice.
| Dose | Route | Model | Outcome | Sources: |
|---|---|---|---|---|
| In vitro | Cell culture | MIA-PaCa-2 pancreatic cancer cells vs BMRPA1 controls | Reported necrosis (not apoptosis) of cancer cells via membrane pores; the leader is what makes the death mode necrotic | PMID 18931881 |
| Animal (IP, ~2 weeks) | Intraperitoneal (nude mice) | Nude-mouse xenografts of BMRPA1.Tuc3, a ras-transformed RAT acinar pancreatic line, not a human xenograft | Reported tumor destruction with sparing of normal cells. A single-lab nude-mouse result; exact mg/kg not stated in the abstract; not human-transferable and not independently confirmed | PMID 16688716 |
| Human | Not applicable | None | No human clinical trial, pharmacokinetic, safety, or efficacy data exists. Sold as research material only; same unapproved class as PNC-27 (FDA-warned, 2017) | ClinicalTrials.gov |
05ChemistryMolecular identity
- Molecular weight
- ≈ 3509 g/mol (3509.1)
- Molecular formula
- C164H255N47O37S
- Monoisotopic mass
- 3506.9238 Da
- PubChem CID
- 16158363
- CAS / UNII
- 392661-17-5 · 5237P710BP
- Human clinical trials
- None (0 registered)
- Sequence (27 aa)
- ETFSDLWKLLKKWKMRRNQFWVKVQRGPubChem CID 16158363
- Structure / class
- Chimeric p53(17–26)–HDM-2-binding peptide + Antennapedia membrane-residency peptide (MRP); shorter PNC-27 analogPMID 18931881
- Construct
- p53 residues 17–26 (ETFSDLWKLL) fused to the same Antennapedia-derived membrane-residency leader as PNC-27 (KKWKMRRNQFWVKVQRG), not classic penetratinPMID 18931881
- Relation to PNC-27
- PNC-27 minus its first five p53 residues (p53 12–16, PPLSQ)PubChem CID 16158363 / 16201774
- Molecular target
- Membrane-localized HDM-2 (MDM2) on cancer cells → transmembrane pore formation / necrosisPMID 18931881 / PMID 20080680
- Half-life
- Not established (no human pharmacokinetic data)Not established
- Regulatory status
- Research chemical; no human trials; not FDA-approved. No PNC-28-specific FDA notice; same class as PNC-27, which the FDA warned against (2017); sold as research material onlyFDA / ClinicalTrials.gov
- Evidence tier
- Preclinical only (in vitro + nude mice); single research group; no independent replicationResearch literature
06Primary sourcesReferences
- PMID 16688716Michl et al., Int J Cancer 2006;119(7):1577–85 (PNC-28: nude-mouse pancreatic xenograft; IP over ~2 weeks; reported tumor destruction sparing normal cells; in vivo)
- PMID 18931881Bowne et al., Ann Surg Oncol 2008;15(12):3588–3600 (the membrane-residency leader converts death mode from apoptosis to necrosis in pancreatic cancer cells)
- PMID 20080680Sarafraz-Yazdi et al., PNAS 2010;107(5):1918–23 (foundational membrane-HDM-2 mechanism for the PNC-27/PNC-28 class, in vitro)
- FDA safety alert, Jan 2017FDA safety alert (January 2017). Consumers warned not to use PNC-27 (the PNC-28 sibling); sold samples were contaminated with Variovorax paradoxus and Ralstonia insidiosa
- ClinicalTrials.govClinicalTrials.gov. 0 registered trials for PNC-28 (and 0 for PNC-27), verified 2026-06-03
Reviewed by Ki Researcher Team · Research use only · Not medical advice · Updated 2026-09-24