Section 01
What it's used for
Kills cancer cells in lab dishes
In lab dishes, this peptide forms pores in cancer-cell membranes within minutes while sparing normal cells (pancreatic, melanoma, cervical lines; a 2025 study found IC50 12.4 micromolar in cervical cancer cells). Cell-culture, no person.
▸Clinical wording
PNC-27 carries residues 12–26 of the HDM-2-binding domain of p53 joined to a membrane-penetrating leader sequence, and in culture it lyses cancer cells while leaving untransformed cells intact. Immuno-electron microscopy showed PNC-27–HDM-2 complexes assembling into transmembrane pores in MIA-PaCa-2 pancreatic carcinoma, A2058 melanoma and rat BMRPA1.TUC-3 cells at 100–150 µg/mL (25–37.5 µM), forming within 3–10 minutes at 37 °C, with no pores in AG-13145 human fibroblasts. A 2025 report gave an IC50 of 12.4 µM against the cervical cancer line HTB-35 with normal cervical cells spared. All of this is cell-culture evidence; none of it is treatment of a person.
Targets a tumor marker in mice
The peptide targets a protein (HDM2) on tumor-cell surfaces but not normal cells. In mice, it killed leukemia cells and leukemia stem cells while sparing healthy stem cells, the strongest finding here, still mouse and cell-culture work.
▸Clinical wording
The selectivity claim rests on HDM-2 being present in the plasma membrane of tumour cells but not of untransformed cells; in the 2010 PNAS study, transfecting membrane-targeted full-length HDM-2 into untransformed MCF-10-2A cells made those cells susceptible to PNC-27. In acute myeloid leukaemia, an independent group at City of Hope found membrane HDM2 on AML blasts and leukaemia-stem-cell-enriched populations but not on normal haematopoietic stem cells, and reported that PNC-27 given in vivo to mice killed both bulk blasts and leukaemia stem cells in primary and secondary transplants while sparing normal stem-cell activity. A separate 2020 study showed necrosis and lactate dehydrogenase release within 4 hours in the leukaemia lines U937, OCI-AML3 and HL-60. This is the best-supported part of the PNC-27 literature, but it remains cell culture plus mouse work.
Pancreatic cancer, mouse data
Pancreatic cancer cells are the most-studied target here; a 2024 study found it also disrupts cancer-cell mitochondria. In mice, a related peptide shrank transplanted tumors over two weeks, though growth resumed after stopping.
▸Clinical wording
Pancreatic lines, chiefly MIA-PaCa-2, are the most-used model for this peptide family, and a 2024 study reported that PNC-27 also enters those cells and binds mitochondrial membranes, causing mitochondrial disruption, with killing blocked by a monoclonal antibody against the p53-binding site of HDM-2. The published in vivo pancreatic data are for the shorter analogue PNC-28: in nude mice, two weeks of intraperitoneal PNC-28 destroyed simultaneously transplanted BMRPA1.Tuc3 tumours and blocked growth of tumours at a remote site, though tumours resumed slow growth after treatment stopped. No pancreatic cancer patient has been treated with PNC-27 in any published study.
Chemo combination, thin evidence
Evidence is thin, from single experiments. In mice, adding PNC-27 to paclitaxel chemo slowed ovarian tumor growth. A 2023 study found ketone bodies made cancer cells more sensitive to it. Cells from two patients' tumors were also killed.
▸Clinical wording
The evidence here is thin and rests on single experiments. In one 2017 study, ID8 ovarian cancer cells that survived paclitaxel showed increased MDM-2 expression and increased susceptibility to PNC-27, and adding PNC-27 to weekly paclitaxel reduced tumour growth in a mouse model. A 2023 study reported that ketone bodies lowered the IC50 of PNC-27 as well as of rapamycin and methotrexate in cancer cell lines, and a 2015 ex vivo study found PNC-27 cytotoxic to primary cells freshly isolated from two patients' ovarian carcinomas and to chemotherapy-resistant ovarian lines. None of these combinations has been tested in patients, and the work comes from a small set of collaborating groups.
No human trials exist yet
No registered clinical trial and no published human study of PNC-27 exists. Nearly all findings come from cell and mouse work by one small network of labs. It is experimental, not approved, and lab results often fail to hold up in people.
▸Clinical wording
A ClinicalTrials.gov query for PNC-27 as an intervention returned no registered studies, and no published human trial of PNC-27 was found in PubMed or Europe PMC. Every result described above comes from cell culture or mouse experiments, and most of the output originates from one collaborating network around SUNY Downstate, Drexel and NomoCan Pharmaceuticals, with the acute myeloid leukaemia work being the main independent exception. PNC-27 is an experimental compound, not an available or approved cancer treatment, and preclinical selectivity has repeatedly failed to predict clinical benefit for other agents.
Section 02
Mechanism of Action
A tumour-suppressor fragment with a delivery tail
- The peptide copies a piece of the tumour suppressor p53 that docks into its regulator protein.
- A membrane-crossing sequence was attached to carry it into cells and stabilise its helical shape.
- In culture all versions killed human cancer lines but not normal cells or cord-blood stem cells.
- They killed cancer cells lacking p53 as readily as cells with mutant or normal p53.
▸Clinical wording
Chimeric design: p53 residues 12-26 on a penetratin leader
PNC-27 was designed from conformational analysis of the p53 segment that docks into HDM-2. Kanovsky and colleagues synthesised peptides spanning p53 residues 12-26, 12-20 and 17-26, each linked at its carboxyl terminus to the penetratin sequence KKWKMRRNQFWVKVQRG to carry it across membranes and stabilise a helix. All three were cytotoxic to human cancer lines in culture but not to normal cells or cord-blood stem cells, and killed p53-null cancer cells as readily as p53-mutant or wild-type ones. NMR later showed that residues 17-26 fold into the native HDM-2-binding conformation, superimposing on the p53-HDM-2 crystal structure at 1.7-2.5 A rms.
Why it hits cancer cells only
- Cancer cell membranes carried four to ninefold more of the target protein than untransformed lines.
- Total amounts inside the cells were comparable, and p53 itself was absent from every membrane fraction.
- Labelled peptide gathered with that protein at the membrane of cancer cells only.
- Forcing the protein onto normal cell membranes made those cells susceptible as well.
▸Clinical wording
HDM-2 in the plasma membrane as the selectivity switch
Selectivity tracks a protein that is normally intracellular. In membrane fractions of MIA-PaCa-2, TUC-3, MCF-7 and A-2058 cells, HDM-2 was four- to ninefold higher than in untransformed lines, although total cellular HDM-2 was comparable; p53 itself was absent from every membrane fraction. Fluorescent PNC-27 co-localised with HDM-2 at the membrane of cancer cells only, and anti-HDM-2 immunoprecipitation recovered the labelled peptide. Transfecting untransformed MCF-10-2A cells with a membrane-targeted HDM-2-CVVK construct made them susceptible, releasing LDH at over twice background, whereas constructs lacking residues 1-109 — the p53-binding pocket — did not.
Punching holes through the cell membrane
- Electron microscopy with two gold labels resolved ring-shaped structures in treated cancer cell membranes.
- The rings averaged about 34.5 nanometres across and did not appear in treated untransformed fibroblasts.
- Killing was strongest at 37 °C and almost absent at 17 °C, pointing to temperature-dependent clustering.
- Treated cells leaked their contents without the enzymes of programmed cell death rising above background.
▸Clinical wording
Transmembrane pore formation and caspase-independent necrosis
Immuno-scanning electron microscopy with dual gold labels (6 nm for PNC-27, 15 nm for HDM-2) resolved ring-shaped structures in treated cancer cell membranes, lined by roughly 1:1 peptide-HDM-2 complexes, with inner diameters averaging 34.5 ± 5.6 nm; no such pores appeared in treated untransformed fibroblasts. Killing was strongly temperature-dependent, maximal at 37 °C and almost absent at 17 °C, consistent with temperature-independent binding followed by temperature-dependent lateral aggregation. Treated cells released LDH without caspase activity rising above background, and double-labelled peptide showed the intact molecule, not fragments, in cancer cell membranes by 30 minutes.
A second target inside the cell
- Work published in 2024 reported mitochondria swelling, rounding and rupturing within about five minutes of exposure.
- Lysosomes stayed intact, and gold labelling placed the peptide on mitochondrial membranes.
- Normal fibroblasts and untransformed breast epithelial cells showed neither change.
- The authors present membrane binding and mitochondrial damage as parallel contributors, not one ordered sequence.
▸Clinical wording
Mitochondrial membrane disruption as a second intracellular target
Work published in 2024 using live-cell confocal microscopy with MitoTracker dyes and immunogold transmission electron microscopy reported a second site of action. In MIA-PaCa-2 pancreatic carcinoma and A2058 melanoma cells, mitochondria swelled, rounded and then ruptured within about five minutes of exposure while lysosomes remained intact, and immunogold labelling placed PNC-27 on mitochondrial membranes. Normal AG13145 fibroblasts and untransformed MCF-10-2A breast epithelial cells showed neither change. The authors present plasma-membrane HDM-2 binding and mitochondrial disruption as parallel contributors to cell death rather than as a single ordered sequence.
An outside group repeated the finding
- An independent group found the target protein on human and mouse leukaemia blasts but not normal blood stem cells.
- The peptide killed positive primary blasts in the low micromolar range while sparing negative normal cells.
- In mouse transplant experiments median survival rose from 111 to 136.5 days.
- That group called the death necrobiosis rather than apoptosis and traced it through an E-cadherin link.
▸Clinical wording
Independent replication in leukaemia and an E-cadherin link
An independent group found membrane HDM2 on human and mouse AML blasts but not on normal haematopoietic stem cells, with the highest expression in the CD34+CD38- stem-cell-enriched fraction. PNC-27 killed membrane-HDM2-positive primary blasts with IC50 values of 11.6-31.6 µM at 48 hours while sparing membrane-HDM2-negative normal CD34+ cells, and in NSG-SGM3 xenografts median survival rose from 111 to 136.5 days. That group called the death necrobiosis rather than apoptosis and traced it to enhanced binding of membrane HDM2 to E-cadherin, then E-cadherin degradation and membrane poration. Separate work reported necrosis within four hours in U937, OCI-AML3 and HL-60 cells.
Section 03
Biological Pathways
No data for this section yet.
Section 04
Dosage Information
Modified p53 HDM-2 binding domain peptide (MRR leader sequence + p53 residues 12-26)| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| None — no human route established | No PNC-27 trial has ever been registered | There is no human dose. A trial-registry search in August 2026 found zero PNC-27 studies — twenty-six years after the first papers. | Everything below is a dish or a mouse. Nothing fixes a starting amount, a schedule, a route or a ceiling for a person, and no regulator has reviewed one. |
| Intraperitoneal — mice with tumours | Tumour transplants in mice, mostly one group | Animal work used sister peptide PNC-28 from an implanted pump: 10 mg per mouse over two weeks. The 40 mg/kg a day comes from vendors. | A pump in a mouse belly is not an injection into a person, the peptide tested was not PNC-27, and nearly all this work comes from one group. |
| In a dish — cell culture only | Cancer cell lines and cells taken from patients | 25–100 µM in the dish; about 75 µM killed nearly all leukaemia cells. Half of ovarian cells died at 100 µg/mL, uterine at 150 µg/mL. | Concentrations in the fluid around cells that have no barrier, no blood flow and no clearance; a µM figure in a well is not milligrams for a body. |
| Subcutaneous — self-administration | Circulating practice, not a finding | Vendor protocols disagree: 200–300 µg three times a week, or 1–2 mg once a day for 4–6 weeks — roughly 2–29 µg/kg at 70–90 kg. | Two sets of numbers that cannot both be right, neither from a study. The blood level either one produces has never been measured in anyone. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Lyophilised powder
The powder is kept sealed and away from moisture: the reagent catalogue gives 2 years at −80 °C and 1 year at −20 °C. The peptide dissolves in water at a stated 100 mg/ml or more. Peer-reviewed papers describe the synthesis and purity but give no storage conditions.
After reconstitution
The stock solution is held under the same sealed, moisture-free conditions: up to 6 months at −80 °C or up to 1 month at −20 °C.
Section 07
Side Effects & Precautions
PNC-27 has never been given to a person: every safety observation on record comes from cell cultures or mice.
Cancer-cell selectivity is a window, not immunity
The originating lab reports no killing of normal cells. The only fully independent lab to measure dose-response in normal cells found PNC-27 kills them too, at higher concentrations: around 15-20 µM in tumor cells versus above 50 µM in normal cells. A window, not immunity for healthy tissue.
No clinical testing has begun
No clinical trial of PNC-27 is registered anywhere. The developer has stated it has not completed the toxicology required before human testing, has not applied for permission to test in humans, and has not started clinical trials.
No formal toxicology exists
- No GLP toxicology study has been performed, by the developer's own statement.
- No maximum tolerated dose, genotoxicity, or reproductive toxicity study has been published in any species.
- Special populations — pregnancy, children, kidney or liver impairment — have not been studied at all.
Toxicity signs appeared only at the top dose
Some mice at the top dose (100 mg/kg/day) showed weight loss and diarrhea in unpublished tests; other groups tolerated it. A separate toxicity study found none of these signs at any dose, only an isolated elevated liver enzyme reading in the two higher-dose groups. Not peer-reviewed.
Mechanism unsettled, one lab dominates
Three different, conflicting explanations for how PNC-27 kills cells appear in the literature. Most supporting studies come from the lab that invented the peptide and holds patents on it. The one independent study of normal-cell toxicity contradicts the strongest form of the selectivity claim.
Section 08
Regulatory Status
FDA / United States
Not approved; contamination warning issued
On 12 January 2017 the FDA warned patients and providers not to use PNC-27, stating it has not evaluated the peptide's safety or efficacy and has not approved it for any disease. An FDA laboratory found the bacterium Variovorax paradoxus in an inhaled PNC-27 solution, and a later sample contained Ralstonia insidiosa; products were also sold as intravenous, rectal and vaginal preparations.
Clinical development
Preclinical only — no human trials
Published research on PNC-27 is limited to cancer cell-line assays and one mouse xenograft study of the mechanism by which the peptide binds membrane HDM-2 and lyses cancer cells; no Phase 1 safety study or registered human trial has been published. The compound has never had an IND or NDA reviewed by the FDA.
WADA
Falls under category S0 by definition
WADA's S0 — Non-Approved Substances covers any pharmacological substance without current approval by a governmental health authority for human therapeutic use, including compounds still in preclinical development; that definition applies to PNC-27 whether or not it is named individually on the Prohibited List, and the ban runs at all times.
Marketing PNC-27 as a cancer cure does not reflect any regulatory approval, and claims made online about its safety or effectiveness have not been evaluated by the FDA, the EMA or any other medicines regulator — treat product-page claims about this peptide with particular caution.
Section 09
Research Studies
- [1]Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cellsKanovsky M, Raffo A, Drew L, Rosal R, Do T, Friedman FK, Rubinstein P, Visser J, Robinson R, Brandt-Rauf PW, Michl J, Fine RL, Pincus MR · Proceedings of the National Academy of Sciences of the United States of America · 2001
- [2]Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranesSarafraz-Yazdi E, Bowne WB, Adler V, Sookraj KA, Wu V, Shteyler V, Patel H, Oxbury W, Brandt-Rauf P, Zenilman ME, Michl J, Pincus MR · Proceedings of the National Academy of Sciences of the United States of America · 2010
- [3]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 lysisSarafraz-Yazdi E, Mumin S, Cheung D, Fridman D, Lin B, Wong L, Rosal R, Rudolph R, Frenkel M, Thadi A, Morano WF, Bowne WB, Michl J, Pincus MR · Biomedicines · 2022
- [4]The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptideSookraj KA, Bowne WB, Adler V, Sarafraz-Yazdi E, Michl J, Pincus MR · Cancer Chemotherapy and Pharmacology · 2010
- [5]Anti-cancer peptide PNC-27 kills cancer cells by unique interactions with plasma membrane-bound hdm-2 and with mitochondrial membranes causing mitochondrial disruptionKrzesaj P, Adler V, Feinman RD, Miller A, Silberstein M, Sarafraz-Yazdi E, Pincus MR · Annals of Clinical and Laboratory Science · 2024
- [6]Targeting cell membrane HDM2: a novel therapeutic approach for acute myeloid leukemiaWang H, Zhao D, Nguyen LXT, Wu H, Li L, Dong D, Troadec E, Zhu Y, Hoang DH, Stein AS, Ghoda L, Sanchez J, Kortylewski M, Kuo YH, Marcucci G · Leukemia · 2020
- [7]Targeting membrane HDM-2 by PNC-27 induces necrosis in leukemia cells but not in normal hematopoietic cellsThadi A, Lewis L, Goldstein E, Aggarwal A, Khalili M, Steele L, Polyak B, Seydafkan S, Bluth MH, Ward KA, Styler M, Campbell PM, Pincus MR, Bowne WB · Anticancer Research · 2020
- [8]Poptosis or peptide-induced transmembrane pore formation: a novel way to kill cancer cells without affecting normal cellsPincus MR, Silberstein M, Zohar N, Sarafraz-Yazdi E, Bowne WB · Biomedicines · 2024
Section 10
Frequently Asked Questions
In cell culture, yes, repeatedly: it lyses pancreatic, melanoma, leukaemia and other cancer cell lines while sparing normal cells in the same dish, and imaging studies show it forming pores in cancer cell membranes within minutes. In mice, one independent group found it killed acute myeloid leukaemia cells, including leukaemia stem cells, while sparing normal blood stem cells. None of this has been tested in a person with cancer.
No. A ClinicalTrials.gov search in 2026 found zero registered studies of PNC-27, more than two decades after the first papers describing it, and no published human trial appears in PubMed or Europe PMC either. Every result reported for this peptide comes from cell culture or mouse experiments.
It's built from a fragment of p53 that binds a protein called HDM-2, fused to a segment that helps it cross membranes. HDM-2 sits inside normal cells but appears on the outer surface of several cancer cell types studied — four to nine times higher in cancer cell membranes than in untransformed cells in one report — and PNC-27 binds that surface HDM-2 to punch pores in the membrane, proposed as the source of its selectivity.
Only in cell culture, plus mouse work using a related shorter peptide called PNC-28 rather than PNC-27 itself — two weeks of injections destroyed transplanted pancreatic tumours in that study, though growth resumed slowly after treatment stopped. No pancreatic cancer patient has been treated with PNC-27 in any published study.
There is no human dose — no trial has ever set one. In cell culture, concentrations of 25 to 100 micromolar have been used against various cancer lines; in mice, the related peptide PNC-28 was delivered continuously from an implanted pump rather than by injection. Self-administration protocols circulating outside any study disagree with each other roughly tenfold.
Both pair a p53/HDM-2-binding fragment with a membrane-penetrating leader from the same design approach. PNC-28 is the version used in the published mouse pancreatic-tumour experiments; PNC-27 is the version behind most of the cell-culture and leukaemia work. Whether the two behave identically in a living animal hasn't been directly compared in the available sourcing.