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PeptideMostly animalNot FDA approved

PNC-27

PNC-27 (p53 and penetratin chimeric peptide)

Last reviewed October 27, 2026 · 24 sources · Written for general readers · Compare with another compound →

The bottom line

PNC-27 is an experimental peptide that kills cancer cells in lab dishes and shrinks tumors in some mouse studies. It has never been tested in a published human trial, and in 2017 FDA warned cancer patients not to use PNC-27 products after finding bacteria in samples. Choosing unproven remedies instead of standard cancer care is linked to a much higher risk of death.

Where the evidence stands

What it is

PNC-27 is a lab made peptide that joins a piece of the p53 protein, a natural tumor suppressor, to penetratin, a short sequence that helps peptides pass into cells.[1] The p53 piece is amino acids 12 to 26, the part that grabs a protein called HDM-2.[2]

It was designed to target HDM-2 (also called MDM2), a protein that many cancer cells carry on their outer membrane, while normal cells carry little of it.[1][3]

It is an experimental compound studied only in cells and animals. It is not approved, and a PubMed search found no published study that gave it to people.[4][3] Nearly all of the published work comes from the research network that developed it.[3][2]

Even so, it has been sold as a cancer treatment. FDA found products sold as an inhaled mist, an IV solution and suppositories.[5] In 2021 a man in Alabama pleaded guilty to making PNC-27 suppositories in his kitchen and selling them to cancer patients.[6]

Name
PNC-27 (PNC-27 (p53 and penetratin chimeric peptide))
Type
Peptide

What it does in the body

PNC-27 is a lab made peptide that the body does not make. It joins the HDM-2 grabbing piece of p53, a natural tumor suppressor, to a cell entry sequence. In lab dishes it binds HDM-2 sitting on the outer membrane of cancer cells and punches holes in that membrane, so the cells burst.[2][1] What it does inside a human body has never been measured.[4]

This is the biology, area by area. A change measured in the body, like a higher blood level, does not always mean a person feels a benefit. The claims check below covers that.

Cancer cells

Lab finding

In dishes it killed leukemia, cervical, breast, ovarian, colon and pancreatic cancer cells.[11][12][8][13][14][10] It killed nearly 100% of one leukemia cell line that lacks p53, and a look alike control peptide did nothing.[9] Cancer cells with more HDM-2 in their membrane were the ones it killed.[13][2]

Healthy cells

Lab finding

Normal fibroblasts, breast cells, cervical cells, blood vessel lining cells and blood cells carried little membrane HDM-2 and survived treatment in dishes.[1][8][12][13][11] Mouse white blood cells were not harmed either.[9] No one has checked healthy human tissue inside a living body.

Energy and cells

Lab finding

In pancreatic cancer cells, besides opening the outer membrane, PNC-27 disrupted mitochondria, the parts of a cell that make energy.[10]

Blood and bone marrow

Seen in animals

In mouse models of acute myeloid leukemia, a blood cancer, it killed leukemia cells, including stem like leukemia cells, while sparing normal blood forming stem cells.[15]

Tumors in animals

Seen in animals

In mice, the related peptide PNC-28 destroyed pancreatic tumors when given at the same time the tumor cells were implanted, but tumors that were already growing only shrank for a while and then grew back more slowly.[16] In mice with ovarian cancer, adding PNC-27 to the chemotherapy drug paclitaxel slowed tumor growth more than paclitaxel alone.[17]

How it works

Researchers propose that PNC-27 binds HDM-2 on the cancer cell surface and forms pores in the membrane, so the cell bursts (necrosis) instead of dying by the usual programmed route.[1][7]

  • In a 2010 study, many kinds of cancer cells carried HDM-2 in their outer membrane, but several normal cell lines did not. When normal breast cells that resisted PNC-27 were given extra HDM-2 aimed at the membrane, they became easy to kill.[2]
  • Electron microscope images showed ring shaped pores holding PNC-27 and HDM-2 in cancer cell membranes, and no pores in treated normal fibroblasts (connective tissue cells).[1]
  • Glowing tags showed the whole peptide stayed in breast cancer cell membranes as the cells burst, while normal breast cells stayed alive.[8]
  • In a related peptide, PNC-28, the penetratin piece was what caused cancer cells to burst rather than die by apoptosis, the usual programmed cell death.[7]
  • It killed leukemia cells that have no working p53 at all, so its action does not depend on the cell's own p53.[9]
  • In pancreatic cancer cells, PNC-27 also damaged mitochondria, the cell's energy centers.[10]

This mechanism comes from lab studies by a small group of researchers and has not been tested in people.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Kills cancer cells in dishes and some mouse models

  • In lab dishes, PNC-27 made human leukemia cells burst within 4 hours, killed nearly all cells of a leukemia line that lacks p53, and killed cervical cancer cells but not normal cervical cells.[11][9][12]
  • It killed cancer cells grown from the ovarian tumors of two patients, and also chemotherapy resistant ovarian cancer cell lines. A look alike control peptide did nothing.[19] Two ovarian cancer lines with high membrane HDM-2 died quickly, while blood vessel lining cells with little HDM-2 were spared.[13]
  • In mice, the related peptide PNC-28 fully destroyed pancreatic tumors when it was given into the belly at the same time as the tumor cells. Tumors that were already growing shrank for a while and then grew back more slowly than in untreated mice.[16]
  • In mouse models of acute myeloid leukemia (AML), it killed leukemia cells while sparing normal blood stem cells.[15]
  • In mice with ovarian cancer, adding it to paclitaxel reduced tumor growth more than paclitaxel alone.[17]
  • A review by the developers reports that PNC-27 and PNC-28 treated an aggressive pancreatic tumor and human AML in mice without obvious side effects.[3]

Limit: Many compounds that kill cancer in dishes and mice fail in people, and nearly all of this work comes from one research network.

Human studies

No human studies

  • A PubMed search returned 26 papers about PNC-27 and PNC-28. None reported giving the peptide to people. Reviews describe only cell and animal work.[4][3]
  • The closest thing to human data is lab work on tumor cells taken from two patients and grown in dishes. That is not a clinical trial.[19]
  • People have still used it. FDA described products sold to cancer patients as an inhaled mist, an IV solution and suppositories, but no one has published what happened to them.[5][6]

Limit: There is no evidence that PNC-27 is safe or works against any cancer in people.

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Cures or treats cancer

Only in animals

Only shown in cells and mice. A related peptide, PNC-28, destroyed pancreatic tumors in mice when given at the same time the tumors were implanted, but tumors that were already growing only shrank for a while and then grew back more slowly.[16] PNC-27 killed leukemia cells in mouse models of AML.[15] No published study has tested PNC-27 in people with cancer.[4] FDA says it has not been shown safe or effective for any disease.[5]

Kills only cancer cells and spares healthy ones

Only in animals

In lab dishes it killed leukemia, cervical, breast and ovarian cancer cells while normal blood, cervical, breast and blood vessel cells survived.[11][12][8][13] In mice with colon tumors, tumor nodules died but normal tissue did not.[14] No one has checked this in people.

Works on many kinds of cancer

Only in animals

It has killed six types of cancer cells in dishes, but the only animal tumor studies involved pancreatic tumors, leukemia, ovarian cancer and colon nodules.[16][15][17][14] It works only on cells with HDM-2 in their outer membrane, so it would not be expected to touch every cancer.[2][13]

Kills cancer stem cells

Only in animals

In mouse models of acute myeloid leukemia, it killed leukemia cells, including stem like leukemia cells, while sparing normal blood stem cells.[15] It also killed stem like colon cancer cells in the lab.[14]

Boosts chemotherapy

Only in animals

In ovarian cancer cells and mice, adding PNC-27 to the chemotherapy drug paclitaxel slowed tumor growth more than paclitaxel alone.[17] In a 2023 dish study, ketone bodies made PNC-27 and some cancer drugs work at lower strengths.[18] This has never been tested in patients.

Is safe with no side effects

Not tested

No study has measured its safety in people.[4] FDA lab tests found bacteria in two PNC-27 samples in 2017, which can cause serious infections.[5]

Known risks and side effects

  • Not a cancer treatment. In a large U.S. cancer database study, people with curable cancers who chose alternative medicine alone had about 2.5 times the risk of death of matched patients who had standard treatment.[20]
  • Contaminated and homemade products. In 2017 FDA labs found two different bacteria in samples of a PNC-27 inhaled solution, a serious danger for people with weak immune systems, as many cancer patients have.[5] In a 2021 federal case, PNC-27 suppositories were made in a home kitchen and warehouse that were not sterile, and some customers found hair in them.[6]
  • Unknown human safety. PNC-27 works by punching holes in cell membranes, and its effects on normal human tissue have never been studied in people.[1][3]
  • Unregulated products. Falsified peptide drugs can contain the wrong ingredient, the wrong amount, nothing active, or toxic contaminants.[21]
  • Sport drug testing. WADA bans substances with no government approval for human use, and its 2027 list names peptides among its examples. That rule appears to cover PNC-27.[22][23]

Regulatory status

Today: PNC-27 is not approved by FDA for any use. FDA has warned cancer patients not to buy or use PNC-27 products, and the peptide does not appear on FDA's 503A compounding nomination list.[5][24] Making and selling it as a cancer treatment has led to a federal criminal case.[6]

  1. FDA warned cancer patients not to use PNC-27 products after its lab found bacteria in an inhaled solution sample.[5]
  2. FDA updated the warning after finding a second type of bacteria in another sample.[5]
  3. An Alabama man pleaded guilty in federal court to conspiracy to sell adulterated and misbranded drugs, homemade PNC-27 suppositories marketed as a cancer treatment.[6]

Sources

  1. Sarafraz-Yazdi E, Mumin S, Cheung D, et al. 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
  2. Sarafraz-Yazdi E, Bowne WB, Adler V, Sookraj KA, Wu V, Shteyler V, et al. 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):1918-1923. PMID 20080680
  3. Pincus MR, Silberstein M, Zohar N, et al. 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
  4. PubMed search for PNC-27 OR PNC-28 OR "p53-penetratin". National Library of Medicine. Searched October 2026; 26 results, none reporting a study in people. PubMed search
  5. U.S. Food and Drug Administration. FDA warns cancer patients not to use PNC-27 products for treatment. January 10, 2017; updated March 27, 2017. FDA warning
  6. U.S. Attorney's Office, Northern District of Alabama. Birmingham Man Pleads Guilty to Conspiracy for Making Unapproved Drug Products in His Kitchen and Warehouse. U.S. Department of Justice press release. January 7, 2021. U.S. DOJ
  7. Bowne WB, Sookraj KA, Vishnevetsky M, et al. 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):3588-3600. PMID 18931881
  8. 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):325-331. PMID 20182728
  9. Davitt K, Babcock BD, Fenelus M, Poon CK, Sarkar A, Trivigno V, et al. 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):241-248. PMID 25117093
  10. Krzesaj P, Adler V, Feinman RD, et al. 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
  11. Thadi A, Lewis L, Goldstein E, et al. 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
  12. Krzesaj PK, Seydafkan S, Miller AI, et al. 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
  13. Thadi A, Gleeson EM, Khalili M, Shaikh MF, Goldstein E, Morano WF, et al. 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
  14. Thadi A, Morano WF, Khalili M, Babcock BD, Shaikh MF, Foster DS, et al. 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
  15. Wang H, Zhao D, Nguyen LX, et al. Targeting cell membrane HDM2: A novel therapeutic approach for acute myeloid leukemia. Leukemia. 2020;34(1):75-86. PMID 31337857
  16. Michl J, Scharf B, Schmidt A, Huynh C, Hannan R, von Gizycki H, et al. 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):1577-1585. PMID 16688716
  17. Alagkiozidis I, Gorelick C, Shah T, Chen YA, Gupta V, Stefanov D, et al. 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
  18. Miller AI, Diaz D, Lin B, Krzesaj PK, Ustoyev S, Shim A, et al. Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents. Biomedicines. 2023;11(9):2515. PMID 37760956
  19. Sarafraz-Yazdi E, Gorelick C, Wagreich AR, Salame G, Angert M, Gartman CH, et al. 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):650-658. PMID 26663795
  20. Johnson SB, Park HS, Gross CP, et al. Use of Alternative Medicine for Cancer and Its Impact on Survival. J Natl Cancer Inst. 2018;110(1). PMID 28922780
  21. Janvier S, De Spiegeleer B, Vanhee C, et al. Falsification of biotechnology drugs: current dangers and/or future disasters? J Pharm Biomed Anal. 2018;161:175-191. PMID 30165334
  22. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. In force January 1, 2026. WADA 2026 List
  23. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2027, section S0 Non-approved substances. In force January 1, 2027. WADA 2027 List
  24. U.S. Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act. Updated May 14, 2026. FDA
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

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