PNC-28
Shorter PNC-27 analog · p53/HDM-2-derived · preclinical only
PNC-28 is a shorter sibling of PNC-27 that works on the same clever principle: the same membrane-anchoring leader, attached to a slightly smaller fragment of the tumor-suppressor p53 (residues 17–26). Like PNC-27, it is designed to exploit a surface quirk of cancer cells — the protein HDM-2 displayed on their outer membrane — binding it and then forming pores that rupture the cell by necrosis while sparing normal cells. PNC-28's most striking result is in animals: in nude mice carrying human pancreatic tumors, the originating group reported that intraperitoneal PNC-28 over about two weeks destroyed the tumors while sparing normal tissue — a notable demonstration of the membrane-lysis approach in a living animal. Context, stated plainly: it is a mouse result from essentially one laboratory, not independently reproduced, with no human trials, safety, efficacy, or dose. PNC-28 is sold only as research material and is unapproved (its sibling PNC-27 drew a 2017 FDA safety alert; details under Safety). This page reports what the preclinical research shows and makes no therapeutic claim: PNC-28 is not a cancer treatment.
The short version
PNC-28 is a close sibling of PNC-27, built on the same elegant idea: exploit a marker (the protein HDM-2) that its researchers say sits on the outer surface of cancer cells but not normal ones, grab onto it, and physically tear holes in the membrane so the cancer cell bursts — leaving normal cells alone. PNC-28 just uses a slightly shorter piece of the p53 protein.
Its standout result is in mice: the originating lab reported that injecting PNC-28 into mice with human pancreatic tumors cleared the tumors over about two weeks while sparing healthy tissue — a striking demonstration of the approach in a living animal.
The honest context: that is a mouse result, from one laboratory, never independently reproduced and never tested in people — so there is no proven human benefit and no established dose. It is sold only as a research chemical, and its sibling PNC-27 drew an FDA warning in 2017. A genuinely interesting approach to watch, not a treatment to use — and nothing here is a dose or medical advice.
Molecular identity
Specs
- 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
Plain English
Mechanism
PNC-28 is a 27-amino-acid chimeric peptide: residues 17–26 of human p53 (ETFSDLWKLL) joined to the same 17-residue Antennapedia-derived membrane-residency leader used in PNC-27 (KKWKMRRNQFWVKVQRG). In other words, it is PNC-27 with its first five p53 residues (PPLSQ, p53 12–16) removed. As with PNC-27, the leader is sometimes loosely called 'penetratin' but is not the classic penetratin sequence (RQIKIWFQNRRMKWKK).
The proposed mechanism is the same as PNC-27's: PNC-28 binds HDM-2 (MDM2) that the originating group reports is aberrantly present in the plasma membrane of cancer cells; the peptide then forms transmembrane pores and the cancer cell dies by necrosis (lactate-dehydrogenase release), sparing normal cells. A defining 2008 study reported that the membrane-residency leader is precisely what converts the death mode from apoptosis (driven by the p53 fragment alone) to this membrane-pore necrosis in pancreatic cancer cells, with the labeled peptide localizing to cancer-cell (but not normal-cell) membranes. The group's controls underline the design: the p53 fragment without the leader drives apoptosis, and a scrambled-p53 version with the leader is inactive.
The same two caveats apply as for PNC-27: this membrane-HDM-2 model is essentially one laboratory's and is not independently confirmed, and all of it — including the pancreatic-tumor result — is in cells and mice, never in a person.
From the studies
Side effects from research
There is no controlled human safety data for PNC-28 — no clinical trial, no pharmacokinetics, no human toxicology. Its studies were animal and cell efficacy experiments, not human safety studies, so nothing about it has been shown to be safe in people.
While the FDA's 2017 safety alert named PNC-27 specifically (after sold samples were found bacterially contaminated — Variovorax paradoxus and Ralstonia insidiosa), PNC-28 is the same chemical class sold through the same unapproved 'research peptide' channels, with the same absence of human data and the same non-sterile, unregulated-product risks — contamination, infection, and immune reactions among them. A fatal gastrointestinal-hemorrhage case report exists for PNC-27 during unapproved use; no comparable PNC-28 case is published, but the shared market and total lack of human safety data mean the same caution applies.
PNC-28 is not an approved drug anywhere credible; it is sold strictly as 'research use only.' This page reports the research and regulatory record only and makes no therapeutic claim — in particular, the striking nude-mouse pancreatic-tumor result is an animal finding and is not a claim that PNC-28 treats, eradicates, or cures cancer in people, and this page does not provide a way to use it.
As reported in literature
Research dosing ranges
This is the evidence that exists for PNC-28 — cell-culture and mouse studies only, from essentially one group, with no independent replication and no human data. The animal amounts are research doses given to mice by intraperitoneal injection; they are not human doses and cannot be converted into one.
| 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 human pancreatic xenografts (BMRPA1.TUC-3 / MIA-PaCa-2) | 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 | — | 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 |
Quick answers
Frequently asked
Does PNC-28 cure pancreatic cancer?
No — that overstates a mouse experiment. In nude mice with human pancreatic tumors, one laboratory reported that PNC-28 destroyed the tumors. That is a preclinical animal result, not a human one: it has not been independently reproduced and has never been tested in a human trial. There is no proof of human benefit, so it is not a cancer treatment.
How is PNC-28 different from PNC-27?
They share the same membrane-anchoring leader. PNC-28 is the shorter one: it uses p53 residues 17–26, while PNC-27 uses 12–26 — so PNC-28 is essentially PNC-27 minus its first five p53 residues. Both are proposed to work the same way and both are preclinical-only with no human data.
Are there human clinical trials of PNC-28?
No. ClinicalTrials.gov returns zero registered trials for PNC-28 (and zero for PNC-27). There is no published human efficacy, safety, or pharmacokinetic data.
Is PNC-28 safe? Did the FDA warn about it?
There is no human safety data. The FDA's 2017 warning specifically named PNC-27, not PNC-28 — but PNC-28 is the same class of unapproved research peptide, sold the same way, so the same concerns (no proven safety, possible contamination) apply. It is not an FDA-approved drug.
Is there a dose or protocol for PNC-28?
No human dose exists, and this page does not provide one. The only amounts in the literature are research doses given to mice by intraperitoneal injection over about two weeks; they are not human doses and cannot be converted into one.
Primary sources
References
- 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 2026-06-04