PNC-27

Dosing from the Literature

Published for cancer: mouse doses only — 40 mg/kg a day into the belly for three weeks, or 40 or 100 mg/kg a day for two weeks, in mice carrying human leukemia cells (Wang et al., 2020). Not published: any dose given to a person, and any measurement of how much of a dose reaches the blood or how long it lasts there.

The table records the amounts each study used, with the species or the cells they were used on. Cell-culture concentrations are the amount in the dish, not a dose. No figure below was given to a person (PubMed and Europe PMC, October 4, 2026).

What It Is

PNC-27 is a synthetic peptide of 32 amino acids, 4032 Da, CAS 1159861-00-3 (PubChem). Its first 15 residues are residues 12–26 of the human p53 protein — Pro-Pro-Leu-Ser-Gln-Glu-Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu, the stretch of p53 that binds the HDM-2 protein (UniProt P04637; Sarafraz-Yazdi et al., 2022). Joined to the far end is a 17-residue leader, Lys-Lys-Trp-Lys-Met-Arg-Arg-Asn-Gln-Phe-Trp-Val-Lys-Val-Gln-Arg-Gly, which the group’s papers call both “penetratin” and “the membrane residency peptide” and which is there to carry the p53 piece across a cell membrane (Davitt et al., 2014; Pincus et al., 2024). The shorter analog PNC-28 carries p53 residues 17–26 on the same leader (Michl et al., 2006).

It was designed by computer modeling in the group of Matthew Pincus and Josef Michl, who worked at a Veterans Affairs medical center in Brooklyn and SUNY Downstate Medical Center, with co-authors at Columbia University, the National Institutes of Health and the New York Blood Center; the idea was a decoy, a peptide that would cross into the nucleus and occupy HDM-2 in place of p53, freeing p53 to trigger apoptosis (Kanovsky et al., 2001; Pincus et al., 2011; Pincus et al., 2024). That is not what happened. The peptide killed cancer cells by bursting them instead, and killed cell lines in which the p53 gene had been deleted outright, so whatever it does cannot depend on p53 being switched back on (Kanovsky et al., 2001; Davitt et al., 2014). The first paper on it appeared in 2001: three p53 peptides on the same leader, PNC-27 among them, were cytotoxic to human cancer cells in culture and had no effect on the growth of normal cells, including cord-blood stem cells (Kanovsky et al., 2001). A 2D-NMR structure of the 32-residue peptide followed in 2004 (Rosal et al., 2004).

PubMed returns 25 records for “PNC-27” (October 4, 2026). Two are unrelated papers that use those letters for something else. Of the remaining 23 — a count that misses the group’s earliest papers, whose abstracts carry no such name (Kanovsky et al., 2001; Do et al., 2003) — 16 list Matthew Pincus or Josef Michl among their authors; several of the later ones also carry the affiliation of NomoCan Pharmaceuticals, a New York company (Sarafraz-Yazdi et al., 2022; Pincus et al., 2024; Krzesaj et al., 2025). Seven are from other groups: an in-vivo leukemia study at City of Hope National Medical Center (Wang et al., 2020), a study of what makes such peptides prefer tumor cells (Yang et al., 2010), two Iranian papers using the peptide to steer nanoparticles or gene carriers at cancer cells (Rahmani et al., 2022; Mokhtarzadeh et al., 2016), a peptide-manufacturing paper (Rodríguez et al., 2014) and two computational studies of the p53 fragment (Barrientos-Salcedo et al., 2007; Soriano-Correa et al., 2023).

No health authority has approved PNC-27 for anything, and no trial of it has ever been registered anywhere in ClinicalTrials.gov’s records (openFDA and ClinicalTrials.gov, searched October 4, 2026). What exists instead is a market: powder sold as a research chemical, and, in the case FDA described in 2017, a product sold to cancer patients from a website, in forms FDA said might include nebulized and intravenous solutions and suppositories (FDA notice, January 10, 2017). See Legal Status.

Mechanism of Action

Everything below comes from cells, isolated membranes, computer models or mice, and most of it from the group that designed the peptide (searches of October 4, 2026). None of it has been tested in a person.

• HDM-2 in the cell membrane (the central claim) — HDM-2, the protein that normally sits inside the nucleus and marks p53 for destruction, was found by Western blot in the membrane fractions of pancreatic, breast and melanoma cancer lines but at low or undetectable levels in untransformed breast-epithelial, pancreatic-acinar and fibroblast lines (Sarafraz-Yazdi et al., 2010). The same was later reported for ovarian lines by flow cytometry and Western blot (Thadi, Gleeson et al., 2020), for colon lines by flow cytometry (Thadi et al., 2021), and for leukemia lines and leukemia cells taken from patients (Thadi, Lewis et al., 2020; Wang et al., 2020; Pincus et al., 2024). PNC-27 was seen to co-locate with it there. The experiment the designers rest the claim on: untransformed MCF-10-2A breast cells, normally untouched by the peptide, were killed by it once they were made to express full-length HDM-2 with a membrane-targeting tag, and were much less susceptible when the HDM-2 they expressed stayed off the membrane or lacked the p53-binding domain (Sarafraz-Yazdi et al., 2010).
• Pore formation, called “poptosis” — Scanning and transmission electron microscopy of pancreatic cancer cells 3 to 10 minutes after exposure showed rings around holes in the membrane, averaging 34.5 nm across in the 100 pores measured, with gold-labelled antibodies placing PNC-27 and HDM-2 in roughly one-to-one pairs around the rim; fibroblasts treated the same way showed no pores (Sarafraz-Yazdi et al., 2022). The cells release lactate dehydrogenase without raising caspase-3 or annexin V, which is the signature of necrosis rather than apoptosis — reported for PNC-27 in colon cancer cells (Thadi et al., 2021) and leukemia cells (Wang et al., 2020), and for the shorter analog PNC-28 in pancreatic cells (Bowne et al., 2008). The group reports the process has two steps, like the bacterial toxin streptolysin O: binding that happens even at 17 °C, then a temperature-dependent gathering of complexes into pores at 37 °C (Sarafraz-Yazdi et al., 2022).
• The leader does the damage — The isolated p53 12–26 fragment, the leader alone, and the two mixed but unjoined all left cancer cells alive; only the covalently joined peptide killed them (Sarafraz-Yazdi et al., 2022). And when the p53 fragment of the shorter analog PNC-28 was instead delivered inside pancreatic cancer cells from a plasmid, without the leader, those cells died by apoptosis with high caspase-3, not by bursting (Bowne et al., 2008). Energy minimization puts the leader pointing away from the HDM-2 binding pocket, free to line a pore (Sarafraz-Yazdi et al., 2022).
• It acts as the whole molecule, and normal cells break it down — PNC-27 labelled green at one end and red at the other produced combined yellow spots in the membranes of breast cancer cells within 30 minutes, which grew as the cells burst: the intact peptide, not a fragment, was doing the work. The same double-labelled peptide spread evenly over untransformed breast epithelial cells and then faded as it was degraded, and those cells stayed alive (Sookraj et al., 2010).
• Mitochondria as a second site — In pancreatic cancer cells the mitochondria stopped holding MitoTracker dye while the lysosomes kept LysoTracker dye, and immuno-electron microscopy put gold-labelled anti-PNC-27 antibody on the mitochondrial membranes (Krzesaj et al., 2024).
• A second mechanism, from the in-vivo study by another group — The City of Hope group reported that PNC-27 strengthens the binding of membrane HDM-2 to E-cadherin, which is then tagged with ubiquitin and destroyed, and that silencing E-cadherin was itself enough to make leukemia cells burst; it called the pore formation “partially mediated” by that degradation and said the cell death it saw continuing after 24 hours implied a further mechanism (Wang et al., 2020). The designing group reads that study as denying its peptide–HDM-2 complexes any part in the pores, and disputes it, pointing to its own electron micrographs and to its finding that the peptide kills two breast cancer lines that carry no E-cadherin (Sarafraz-Yazdi et al., 2022; Pincus et al., 2024).
• A rival explanation of the selectivity — An independent laboratory found that the selectivity travels with the leader peptide, not the p53 part: swapping it for other cell-penetrating sequences abolished the tumor preference, the leader itself bound chondroitin sulfate, and stripping chondroitin sulfate from tumor cells reduced the killing by the peptides it built on that leader. It concluded that chondroitin sulfate, which tumor cells carry more of, is the portal for that whole class of peptides, PNC-27 included. In its hands PNC-27’s half-killing concentrations were only 2–3 times lower in tumor cells than in normal cells, and the peptides it built killed by apoptosis (Yang et al., 2010).
• It does not need working p53 — K562 leukemia cells, which have both copies of the p53 gene deleted, express HDM-2 in their membranes and were killed almost completely, while mouse leukocytes were not (Davitt et al., 2014). The first paper reported the same independence of p53 for colon, breast and osteosarcoma lines whose p53 gene was deleted (Kanovsky et al., 2001).

What the Research Shows

The results below are in cells and in mice. There is no human equivalent to follow them with; the next section records what the literature and the registry hold instead (PubMed and ClinicalTrials.gov, October 4, 2026).

• Leukemia, in mice (the one in-vivo study from outside the designing group) — At City of Hope National Medical Center, HDM-2 was found on the membranes of leukemia blasts from patients, including the stem-cell-enriched fraction, but not on normal blood stem cells. Mice carrying a patient’s leukemia and treated with 40 mg/kg into the belly daily for three weeks lived a median 136.5 days against 115 days on the control peptide and 111 on vehicle; marrow transplanted on from the treated mice into a second set of mice gave 156.5 days against 93. In a mouse-derived leukemia model the figures were 54 days against 41 and 42. Healthy mice given 100 mg/kg daily for two weeks showed no change in blood counts and their marrow stem cells still rebuilt the blood of other mice (Wang et al., 2020).
• Pancreatic cancer, in mice — but with the shorter analog — Nude mice carrying a transplanted rat pancreatic carcinoma were infused with PNC-28 from an implanted pump for two weeks: the tumors were destroyed, while tumors in the control-peptide group grew to about 3500 mg and spread. Treatment started later shrank established tumors, which then regrew slowly (Michl et al., 2006; Pincus et al., 2024). This experiment used PNC-28, not PNC-27.
• Colon and ovarian cancer, in mice — In colon cancer models imaged by bioluminescence, PNC-27 was reported to cause necrosis of tumor nodules and not of normal tissue (Thadi et al., 2021). Added to weekly paclitaxel in a mouse model of ovarian cancer, it significantly reduced tumor growth; in culture, mouse ID8 ovarian cancer cells (Cellosaurus CVCL_IU14) — the line used in that model — carried more MDM-2 on their surface after surviving paclitaxel and were more easily killed by the peptide (Alagkiozidis et al., 2017).
• Cells from patients — Cells grown out of two freshly removed ovarian cancers, one mucinous and one high-grade serous, were killed in a dose-dependent way while the control peptide did nothing (Sarafraz-Yazdi et al., 2015). Half of the leukemia blasts from 12 patients, chosen because they carried HDM-2 on their membranes, were killed at 11.64–31.64 µM over 48 hours, while blood stem cells from 9 healthy donors, which lack it, were barely touched (Wang et al., 2020). These were cells in a dish; none of the patients received the peptide.
• Which cell lines, and which were spared — Across the group’s studies PNC-27 and its shorter analog PNC-28 killed pancreatic, breast, ovarian, colon, cervical, lung, sarcoma and leukemia lines at 6–80 µM, including multi-drug-resistant OVCAR-3 cells and CD44-positive colon cancer stem cells, while leaving fibroblasts, pancreatic acinar cells, breast epithelial cells, keratinocytes, umbilical-vein endothelial cells and rat mononuclear cells alive at the highest concentrations used (Pincus et al., 2024; Thadi, Gleeson et al., 2020; Thadi et al., 2021). Melanoma cells were killed in a dose-dependent way in the same group’s earlier work (Sarafraz-Yazdi et al., 2010). Half of a cervical cancer line’s cells were killed at 12.4 µM, and a normal cervical line was not (Krzesaj et al., 2025).
• Other uses of the molecule — Outside the cancer-killing work, groups in Iran have used PNC-27 as a homing label: bolted to iron-oxide nanoparticles it collected in and around cells expressing HDM-2 and not in a normal mouse fibroblast line (Rahmani et al., 2022), and attached to a polymer it carried genes into cancer cells (Mokhtarzadeh et al., 2016).
• Things that made it work better in a dish — Lithium acetoacetate, a ketone-body salt, cut the concentration of PNC-27 needed to kill half of MCF-7 breast cancer cells almost fourfold (Miller et al., 2023). Mouse ID8 ovarian cancer cells that had survived paclitaxel were more easily killed by PNC-27 (Cellosaurus CVCL_IU14; Alagkiozidis et al., 2017).

Human Data

There is none. No published study has given PNC-27, or its analog PNC-28, to a person, and no trial of either has ever been registered (PubMed and Europe PMC searched October 4, 2026; ClinicalTrials.gov searched the same day for “PNC-27”, “PNC27”, “PNC-28”, “poptosis”, “membrane HDM-2” and the developer’s company name, with no records).

• What is published instead — Human cells, not human beings: cancer cell lines, cells grown out of two ovarian tumors removed in surgery (Sarafraz-Yazdi et al., 2015), leukemia blasts and normal blood stem cells from patients and donors (Wang et al., 2020), and a normal cervical cell line (Krzesaj et al., 2025). Work on cells taken from a patient is laboratory work; it says nothing about what the peptide does once it is in a body.
• No pharmacokinetics — Nothing is published on how much of a dose reaches the blood, how fast it is broken down, or where it goes, in people or in animals (PubMed, October 4, 2026). The leukemia study from outside the designing group noted in 2020 that pharmacokinetic and dose-finding modeling was under way (Wang et al., 2020); nothing has been published since.
• What FDA found in the market — In January 2017 an FDA laboratory found the bacterium Variovorax paradoxus in a sample of PNC-27, which FDA describes as “an unapproved drug product promoted as a treatment or cure for cancer” (FDA, 2017). FDA’s notice of January 10, 2017 named the website that promoted and sold it, said PNC-27 may be available as a nebulized solution, an intravenous solution or a vaginal or rectal suppository, stated that the agency had not evaluated or approved it as safe and effective to treat any disease, and said it had received no reports of illnesses or serious adverse events (FDA notice, January 10, 2017). Those products were not part of any study, and no published analysis of one exists.
• Why the evidence meter reads “Animal only” — The meter counts published human data on the compound itself for the use on its card. For PNC-27 that count is zero. Mouse survival curves, however striking, are mouse survival curves (Wang et al., 2020).

Reconstitution & Storage

No label and no trial document exists for PNC-27, so there is no authoritative statement of how it is prepared, stored or given: it has never been given to a person in a published study. What follows is what the suppliers’ own product pages state, read on October 4, 2026, and what FDA found when it tested a product.

• The form sold — A laboratory-reagent supplier’s product page describes a “sterile filtered white lyophilized (freeze-dried) powder”, greater than 97% pure by RP-HPLC, in 5, 25 and 100 mg vials, and states that its products are “furnished for LABORATORY RESEARCH USE ONLY”. A bulk-chemical trading listing offers 5 and 10 mg vials of 99% purity by HPLC while the same page’s title calls the peptide one “used for cancer treatment”.
• Storage, as the supplier states it — The same reagent page says the lyophilized powder is “stable at room temperature for 3 weeks” and otherwise kept desiccated below −18 °C, and that once dissolved it is kept at 4 °C for 2–7 days or below −18 °C for longer. No independent stability study of PNC-27 has been published (PubMed, October 4, 2026).
• What a lab report can show — Its mass is 4032 Da and its formula C188H293N53O44S (PubChem); a reagent supplier prints 4031.72 Da. COA Check reads a lab report and says which of those a document actually establishes.
• Sterility is the documented failure — Purity on a certificate is not sterility. FDA’s laboratory found Variovorax paradoxus in a sample of a PNC-27 solution for inhalation sold for cancer, and in an update of March 27, 2017 a different bacterium, Ralstonia insidiosa, in a second inhalation sample; FDA’s notice warned that a contaminated product carries a risk of serious, potentially life-threatening infection (FDA, 2017; FDA notice, January 10, 2017).

→ Peptide Calculator — vial-to-syringe math

Side Effects & Risks

• In people — Nothing is known. No published study, case report or registry record describes a person given PNC-27 (PubMed, Europe PMC and ClinicalTrials.gov, searched October 4, 2026).
• In mice, at the doses the leukemia study used — Seven healthy mice given 100 mg/kg into the belly daily for two weeks showed no significant difference from seven vehicle-treated mice in white-cell, hemoglobin or platelet counts, marrow and spleen cell counts, or the stem-cell fraction, and their marrow stem cells rebuilt the blood of other mice normally (Wang et al., 2020). Mice infused with the analog PNC-28 for two weeks thrived and gained weight no differently from untreated mice, as the designing group’s review reports that experiment (Pincus et al., 2024).
• No toxicology package — No formal toxicology study, no reproductive or pregnancy study and no drug-interaction study of PNC-27 turned up in searches for this page (PubMed and Europe PMC, October 4, 2026). The longest exposure in the studies whose methods could be read is three weeks (Wang et al., 2020).
• The selectivity is the whole safety argument, and it is contested — The case that PNC-27 spares normal cells rests on cell lines that carry little membrane HDM-2 (Sarafraz-Yazdi et al., 2010; Pincus et al., 2024). An independent laboratory measured only a 2–3 fold difference between tumor and normal cells and traced the preference to the leader peptide binding chondroitin sulfate, which tumor cells carry more of (Yang et al., 2010). A membrane-bursting peptide with a narrow margin is a different proposition from one with a wide one. No formal toxicology study has been published; the in-vivo papers report the blood counts and marrow function above in healthy mice (Wang et al., 2020) and no necrosis of normal tissue in a colon cancer model (Thadi et al., 2021).
• Contamination, the one documented harm pathway — FDA found bacteria in a sample of a solution for inhalation, and in an update of March 27, 2017 a different bacterium, Ralstonia insidiosa, in a second inhalation sample; it warned of the risk of serious, potentially life-threatening infection, and named people with weakened immune systems among those at higher risk, with young children, elderly people and pregnant women (FDA, 2017; FDA notice, January 10, 2017). No illnesses had been reported to FDA at that point.
• Delay — Besides direct harm, FDA names an indirect harm for illegally sold cancer products: delaying or interfering with proven, beneficial treatments — time spent on an unproven product instead of one with evidence behind it (FDA, 2017).
• WADA — PNC-27 is not named on the 2026 Prohibited List. Section S0 prohibits at all times any pharmacological substance not addressed by another section “with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued…)” (World Anti-Doping Agency, 2026). No government has approved PNC-27, so S0 covers it.

Bloodwork & Monitoring

No monitoring guidance for PNC-27 has been published, because no person has been given it in a published study and no trial has been registered (PubMed and ClinicalTrials.gov, October 4, 2026). The animal and cell studies measured these:

• Blood counts in mice — White-cell, hemoglobin and platelet counts, marrow and spleen cell counts, and the marrow stem-cell fraction, in healthy mice given the peptide for two weeks (Wang et al., 2020).
• Leukemia burden in mice — The share of human leukemia cells in blood, marrow and spleen, and survival (Wang et al., 2020).
• Lactate dehydrogenase release — The laboratory read-out used throughout this literature to tell bursting from orderly cell death, measured in the culture medium, not in blood (Bowne et al., 2008; Thadi, Lewis et al., 2020).
• Membrane HDM-2 — Measured by flow cytometry and Western blot on cells, and proposed by its developers as the marker that decides whether a cancer cell is susceptible (Thadi, Gleeson et al., 2020). The leukemia study from outside the designing group found that the peptide’s killing of cultured leukemia cells from patients tracked with how much of it the cells carried (Wang et al., 2020). No blood test for it is in clinical use.
• Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

No study has tested PNC-27 with any compound on this site (PubMed and Europe PMC, searched October 4, 2026). Two published combinations exist, both with cancer drugs or metabolites rather than peptides, and both in cells or mice.

→ Peptide Calculator — vial-to-syringe math

Legal Status

Related Compounds

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Next Steps

References

1. National Library of Medicine. PubChem: PNC-27, CID 16201774 (C188H293N53O44S, 4032 g/mol; CAS 1159861-00-3). pubchem.ncbi.nlm.nih.gov. Read October 4, 2026.
2. UniProt Consortium. P04637 (P53_HUMAN), cellular tumor antigen p53, 393 residues; residues 12–26 read PPLSQETFSDLWKLL. rest.uniprot.org/uniprotkb/P04637. Read October 4, 2026.
3. Cellosaurus (SIB Swiss Institute of Bioinformatics). ID8, CVCL_IU14 (synonym ID8/MOSEC): species of origin Mus musculus (mouse); derived from the surface epithelium of the ovary, C57BL/6, adult female; a spontaneously immortalized cell line. cellosaurus.org/CVCL_IU14. Read October 5, 2026.
4. Kanovsky 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. Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells. Proc Natl Acad Sci U S A. 2001;98(22):12438-43. PMID: 11606716. DOI: 10.1073/pnas.211280698. (Read October 5, 2026: the peptide named PNC-27, its sequence and the penetratin leader, the cytotoxicity to cancer but not normal cells, and the p53-null lines.)
5. Do TN, Rosal RV, Drew L, Raffo AJ, Michl J, Pincus MR, Friedman FK, Petrylak DP, Cassai N, Szmulewicz J, Sidhu G, Fine RL, Brandt-Rauf PW. Preferential induction of necrosis in human breast cancer cells by a p53 peptide derived from the MDM2 binding site. Oncogene. 2003;22(10):1431-44. PMID: 12629507. DOI: 10.1038/sj.onc.1206258. (The same p53 12-26 peptide on the same carrier, under the name p53(15)Ant.)
6. Rosal R, Pincus MR, Brandt-Rauf PW, Fine RL, Michl J, Wang H. NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells. Biochemistry. 2004;43(7):1854-61. PMID: 14967026. DOI: 10.1021/bi035718g.
7. Michl J, Scharf B, Schmidt A, Huynh C, Hannan R, von Gizycki H, Friedman FK, Brandt-Rauf P, Fine RL, Pincus MR. PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo. Int J Cancer. 2006;119(7):1577-85. PMID: 16688716. DOI: 10.1002/ijc.22029.
8. Bowne WB, Sookraj KA, Vishnevetsky M, Adler V, Sarafraz-Yazdi E, Lou S, Koenke J, Shteyler V, Ikram K, Harding M, Bluth MH, Ng M, Brandt-Rauf PW, Hannan R, Bradu S, Zenilman ME, Michl J, Pincus MR. The penetratin sequence in the anticancer PNC-28 peptide causes tumor cell necrosis rather than apoptosis of human pancreatic cancer cells. Ann Surg Oncol. 2008;15(12):3588-600. PMID: 18931881. DOI: 10.1245/s10434-008-0147-0.
9. Sarafraz-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. Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes. Proc Natl Acad Sci U S A. 2010;107(5):1918-23. PMID: 20080680. DOI: 10.1073/pnas.0909364107.
10. Sookraj KA, Bowne WB, Adler V, Sarafraz-Yazdi E, Michl J, Pincus MR. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer Chemother Pharmacol. 2010;66(2):325-31. PMID: 20182728. DOI: 10.1007/s00280-009-1166-7.
11. Yang H, Liu S, Cai H, Wan L, Li S, Li Y, Cheng J, Lu X. Chondroitin sulfate as a molecular portal that preferentially mediates the apoptotic killing of tumor cells by penetratin-directed mitochondria-disrupting peptides. J Biol Chem. 2010;285(33):25666-76. PMID: 20484051. DOI: 10.1074/jbc.M109.089417.
12. Pincus MR, Fenelus M, Sarafraz-Yazdi E, Adler V, Bowne W, Michl J. Anti-cancer peptides from ras-p21 and p53 proteins. Curr Pharm Des. 2011;17(25):2677-98. PMID: 21728981. DOI: 10.2174/138161211797416075.
13. Davitt K, Babcock BD, Fenelus M, Poon CK, Sarkar A, Trivigno V, Zolkind PA, Matthew SM, Grin’kina N, Orynbayeva Z, Shaikh MF, Adler V, Michl J, Sarafraz-Yazdi E, Pincus MR, Bowne WB. 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. Ann Clin Lab Sci. 2014;44(3):241-8. PMID: 25117093.
14. Sarafraz-Yazdi E, Gorelick C, Wagreich AR, Salame G, Angert M, Gartman CH, Gupta V, Bowne WB, Lee YC, Abulafia O, Pincus MR, Michl J. Ex vivo efficacy of anti-cancer drug PNC-27 in the treatment of patient-derived epithelial ovarian cancer. Ann Clin Lab Sci. 2015;45(6):650-8. PMID: 26663795.
15. Mokhtarzadeh A, Parhiz H, Hashemi M, Abnous K, Ramezani M. P53-derived peptides conjugation to PEI: an approach to producing versatile and highly efficient targeted gene delivery carriers into cancer cells. Expert Opin Drug Deliv. 2016;13(4):477-91. PMID: 26654047. DOI: 10.1517/17425247.2016.1126245.
16. Alagkiozidis I, Gorelick C, Shah T, Chen YA, Gupta V, Stefanov D, Amarnani A, Lee YC, Abulafia O, Sarafraz-Yazdi E, Michl J. Synergy between paclitaxel and anti-cancer peptide PNC-27 in the treatment of ovarian cancer. Ann Clin Lab Sci. 2017;47(3):271-281. PMID: 28667027.
17. Wang H, Zhao D, Nguyen LX, Wu H, Li L, Dong D, Troadec E, Zhu Y, Hoang DH, Stein AS, Al Malki M, Aldoss I, Lin A, Ghoda LY, McDonald T, Pichiorri F, Carlesso N, Kuo YH, Zhang B, Jin J, Marcucci G. Targeting cell membrane HDM2: a novel therapeutic approach for acute myeloid leukemia. Leukemia. 2020;34(1):75-86. PMID: 31337857. DOI: 10.1038/s41375-019-0522-9.
18. Thadi 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. Targeting membrane HDM-2 by PNC-27 induces necrosis in leukemia cells but not in normal hematopoietic cells. Anticancer Res. 2020;40(9):4857-4867. PMID: 32878773. DOI: 10.21873/anticanres.14488.
19. Thadi A, Gleeson EM, Khalili M, Shaikh MF, Goldstein E, Morano WF, Daniels LM, Grandhi N, Glatthorn H, Richard SD, Campbell PM, Sarafraz-Yazdi E, Pincus MR, Bowne WB. Anti-cancer tumor cell necrosis of epithelial ovarian cancer cell lines depends on high expression of HDM-2 protein in their membranes. Ann Clin Lab Sci. 2020;50(5):611-624. PMID: 33067207.
20. Thadi A, Morano WF, Khalili M, Babcock BD, Shaikh MF, Foster DS, Piazza Y, Gleeson EM, Goldstein E, Steele L, Campbell PM, Lin BO, Pincus MR, Bowne WB. Molecular targeting of H/MDM-2 oncoprotein in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells. Anticancer Res. 2021;41(1):27-42. PMID: 33419797. DOI: 10.21873/anticanres.14749.
21. Sarafraz-Yazdi E, Mumin S, Cheung D, Fridman D, Lin B, Wong L, Rosal R, Rudolph R, Frenkel M, Thadi A, Morano WF, Bowne WB, Pincus MR, Michl J. 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. Biomedicines. 2022;10(5):945. PMID: 35625682. DOI: 10.3390/biomedicines10050945. (Full text at PMC9138867, read October 4, 2026: the 32-residue sequence, the pores’ average diameter of 34.5 nm (n = 100), and the dispute with the leukemia study over what lines the pores.)
22. Rahmani R, Darroudi M, Gharanfoli M, Chamani J, Gholamin M, Hashemi M. Conjugated PNC-27 peptide/PEI-superparamagnetic iron oxide nanoparticles (SPIONs) as a double targeting agent for early cancer diagnosis: in vitro study. Iran J Basic Med Sci. 2022;25(10):1234-1242. PMID: 36311203. DOI: 10.22038/IJBMS.2022.65590.14430.
23. Miller AI, Diaz D, Lin B, Krzesaj PK, Ustoyev S, Shim A, Fine EJ, Sarafraz-Yazdi E, Pincus MR, Feinman RD. Ketone bodies induce unique inhibition of tumor cell proliferation and enhance the efficacy of anti-cancer agents. Biomedicines. 2023;11(9):2515. PMID: 37760956. DOI: 10.3390/biomedicines11092515.
24. Soriano-Correa C, Vichi-Ramírez MM, Herrera-Valencia EE, Barrientos-Salcedo C. The role of ETFS amino acids on the stability and inhibition of p53-MDM2 complex of anticancer p53-derivatives peptides: density functional theory and molecular docking studies. J Mol Graph Model. 2023;122:108472. PMID: 37086514. DOI: 10.1016/j.jmgm.2023.108472.
25. Barrientos-Salcedo C, Arenas-Aranda D, Salamanca-Gómez F, Ortiz-Muñiz R, Soriano-Correa C. Electronic structure and physicochemical properties characterization of the amino acids 12-26 of TP53: a theoretical study. J Phys Chem A. 2007;111(20):4362-9. PMID: 17472350. DOI: 10.1021/jp067841y.
26. Rodríguez V, Asenjo JA, Andrews BA. Design and implementation of a high yield production system for recombinant expression of peptides. Microb Cell Fact. 2014;13:65. PMID: 24885242. DOI: 10.1186/1475-2859-13-65.
27. Krzesaj P, Adler V, Feinman RD, Miller A, Silberstein M, Yazdi E, Pincus MR. Anti-cancer peptide PNC-27 kills cancer cells by unique interactions with plasma membrane-bound hdm-2 and with mitochondrial membranes causing mitochondrial disruption. Ann Clin Lab Sci. 2024;54(2):137-148. PMID: 38802154.
28. Pincus MR, Silberstein M, Zohar N, Sarafraz-Yazdi E, Bowne WB. Poptosis or peptide-induced transmembrane pore formation: a novel way to kill cancer cells without affecting normal cells. Biomedicines. 2024;12(6):1144. PMID: 38927351. DOI: 10.3390/biomedicines12061144. (Full text at PMC11201261, read October 4, 2026: the 6–80 µM range, the cell lines killed and spared, and the PNC-28 mouse experiment.)
29. Krzesaj PK, Seydafkan S, Miller AI, Chen HT, Premsrirut P, Shim A, Mcglinchey S, Yazdi E, Brandt-Rauf P, Silberstein M, Jahari G, Feinman RD, Pincus MR. HDM-2-targeting peptide PNC-27 kills cervical cancer cells but not normal cervical cells. Ann Clin Lab Sci. 2025;55(3):347-353. PMID: 40750238.
30. US Food and Drug Administration. Questions and Answers: FDA alerts companies to stop the illegal sale of products claiming to treat cancer. fda.gov/consumers/health-fraud-scams/questions-and-answers-fda-alerts-companies-stop-illegal-sale-products-claiming-treat-cancer (content current as of April 25, 2017). Read October 4, 2026: “in January 2017, an FDA laboratory discovered the bacteria Variovorax paradoxus in a sample of PNC-27, an unapproved drug product promoted as a treatment or cure for cancer.”
31. US Food and Drug Administration. FDA warns cancer patients not to use PNC-27 products for treatment. Drug Safety and Availability, January 10, 2017; updated March 27, 2017 (“Content current as of: 03/27/2017”). FDA’s own address for it no longer resolves; read October 5, 2026 in the Internet Archive copy captured March 7, 2026, at web.archive.org/web/20260307095200/https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-cancer-patients-not-use-pnc-27-products-treatment: the website named, the Variovorax paradoxus sample for inhalation, the dosage forms PNC-27 “may be available in”, the statement that FDA had received no reports of illnesses or serious adverse events, and the update’s second inhalation sample containing Ralstonia insidiosa.
32. US Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated May 14, 2026. fda.gov/media/94155/download. Searched for PNC-27 and PNC-28: no entry.
33. US Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated March 21, 2025. fda.gov/media/94164/download. Searched for PNC-27 and PNC-28: no entry.
34. US Code of Federal Regulations. 21 CFR 216.23 (bulk drug substances that can be used in 503A compounding) and 216.24 (drug products withdrawn or removed because they were found unsafe or not effective). ecfr.gov. Read October 4, 2026: no entry for PNC-27.
35. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org. Read October 4, 2026: PNC-27 is not named.
36. ClinicalTrials.gov. Searches for “PNC-27”, “PNC27”, “PNC-28”, “poptosis”, “membrane HDM-2” and “NomoCan”, October 4, 2026, API v2: no records in any of them.
37. Searches of October 4, 2026: PubMed, “PNC-27” (25 records; 2 about unrelated subjects that use those letters, and of the 23 remaining, 16 list Matthew Pincus or Josef Michl among their authors and 6 are in Annals of Clinical and Laboratory Science); PubMed, “PNC-28” (7 records; six of them are inside the PNC-27 set, the seventh being Michl et al., 2006, the mouse study of PNC-28 itself); Europe PMC, “PNC-27” (the same records, plus unrelated hits for the letters PNC); PubMed for PNC-27 with toxicology, pharmacokinetic, pregnancy, drug-interaction and case-report terms (no records); openFDA Drugs@FDA for “PNC-27” and “PNC 27” (0 applications) and the openFDA NDC directory (no listing); PubChem name search; UniProt P04637; laboratory-reagent and bulk-chemical supplier product pages listing PNC-27 powder for research use only, (supplier and seller pages not named, per site policy).

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