Other compounds

PNC-27

Updated · 24 sources · Editorial policy

PNC-27 is a synthetic 32-amino-acid peptide designed in the early 2000s by a group of researchers from SUNY Downstate, Columbia University and the Brooklyn VA. It joins a short piece of the tumor-suppressor protein p53 to a “cell-penetrating” peptide, and in laboratory experiments it punches holes in the outer membranes of many kinds of cancer cells.

It has been sold online and through alternative-medicine clinics as a cancer treatment. All of the evidence is from cell culture and animal (mostly mouse) studies. No human clinical trial of PNC-27 has been published or registered, and the FDA has not approved it for any use. In 2017 the FDA warned patients not to use PNC-27 products after finding bacteria in them, and in 2021 an Alabama man was sentenced to federal prison for making and selling PNC-27 suppositories as a cancer treatment.

This page summarizes what the laboratory research, the FDA and federal prosecutors report. It is for education only and is not medical advice.

Property Detail
Class Synthetic chimeric peptide (p53 fragment joined to a cell-penetrating peptide); investigational anticancer agent
Size 32 amino acids; C₁₈₈H₂₉₃N₅₃O₄₄S, molecular weight ≈4032 (PubChem)
Proposed target HDM-2 (human MDM2) protein sitting in the outer membrane of cancer cells
Proposed effect Pore formation in the cell membrane, leading to rapid cell death by necrosis
Evidence base Cell culture and mouse studies only; no published human trials
Registered human trials None on ClinicalTrials.gov
Half-life Not established; no pharmacokinetic study found
US status Not FDA-approved for any use; FDA consumer warning in 2017
WADA status Not named; non-approved substances fall under S0 (prohibited at all times)

What it is

The idea behind PNC-27 came from p53, a protein that stops damaged cells from dividing. Inside cells, p53 is held in check by a partner protein called MDM2 (HDM-2 in humans), which grips a short stretch near the front end of p53. In 2001 the developers made peptides copying that MDM2-binding stretch of p53 and attached each one, at its carboxyl (tail) end, to penetratin, a peptide that carries cargo across cell membranes (Kanovsky et al., PNAS 2001).

PNC-27 is the longest of these peptides. It has two parts, with no changed amino acids in either:

  • p53 segment (15 amino acids). An unmodified copy of residues 12–26 of human p53, the region that binds HDM-2.
  • Penetratin segment (17 amino acids). An unmodified stretch of the fruit-fly protein Antennapedia, placed on the carboxyl end (Do et al., Oncogene 2003).

The developers chose penetratin because its many positively charged residues help hold the p53 segment in the helical shape it uses to bind MDM2 (Kanovsky et al., PNAS 2001). NMR studies showed that the peptide forms amphipathic helices, with its water-repelling side chains on one face and its charged side chains on the other. That shape is typical of peptides that can disrupt membranes (Rosal et al., Biochemistry 2004). PubChem lists its formula and a molecular weight of about 4032 (PubChem CID 16201774).

A shorter sister peptide, PNC-28, uses only residues 17–26 of p53 with the same penetratin tail (Michl et al., Int J Cancer 2006). The control peptide in most experiments, PNC-29, is an unrelated sequence on the same penetratin tail.

How it is thought to work

PNC-27 was designed to free p53 inside the cell, but the experiments pointed to a different mechanism. The cells did not die by apoptosis (orderly, programmed cell death), as p53 activation would predict. They died by necrosis: the membrane broke open and the cell contents leaked out, often within hours (Do et al., Oncogene 2003; Bowne et al., Ann Surg Oncol 2008). The peptides also killed cancer cells that make no p53 at all (Kanovsky et al., PNAS 2001; Davitt et al., Ann Clin Lab Sci 2014).

The developers’ current model has these steps:

  1. HDM-2 on the cell surface. The group reported HDM-2 in the outer membranes of a variety of cancer cell lines, but not in several normal cell lines. Normal breast cells became susceptible to PNC-27 when engineered to place HDM-2 on their surface (Sarafraz-Yazdi et al., PNAS 2010).
  2. Binding. An antibody that blocks the p53-binding site of HDM-2 prevented PNC-27 from killing pancreatic cancer cells (Krzesaj et al., Ann Clin Lab Sci 2024).
  3. Pore formation. The intact peptide, not a fragment of it, gathers in the cancer cell membrane (Sookraj et al., Cancer Chemother Pharmacol 2010). Electron microscopy showed ring-shaped pores lined with PNC-27 and HDM-2 in roughly equal numbers. No pores formed in normal fibroblasts treated the same way (Sarafraz-Yazdi et al., Biomedicines 2022).
  4. Mitochondrial damage. The same group later reported that the peptide also binds to and disrupts mitochondria inside cancer cells (Krzesaj et al., Ann Clin Lab Sci 2024).

An independent group at City of Hope proposed a different route in leukemia cells: PNC-27 bound membrane HDM-2 and led to the breakdown of E-cadherin, a membrane adhesion protein, which damaged the membrane (Wang et al., Leukemia 2020).

The penetratin tail matters. When the developers delivered the p53 segment without penetratin, pancreatic cancer cells died by apoptosis rather than necrosis (Bowne et al., Ann Surg Oncol 2008). A Chinese research group found that swapping penetratin for other cell-penetrating peptides removed the preference for tumor cells, and suggested that penetratin’s binding to chondroitin sulfate, a sugar polymer abundant on some tumor cells, explains part of the selectivity (Yang et al., J Biol Chem 2010).

What the research shows

Cell-culture studies

The cancer types tested in cell culture include the following. Nearly all of these studies come from the developers’ network of labs.

Cancer type Model Reported finding Source
Breast Human cancer cell lines vs non-cancerous breast cells Rapid necrosis-like death in cancer cells; minimal toxicity to normal breast cells Do et al., Oncogene 2003
Leukemia p53-null K562 cell line vs mouse white blood cells Near-complete killing of K562 cells; no effect on control cells Davitt et al., Ann Clin Lab Sci 2014
Ovarian Cancer cells freshly isolated from 2 patients’ tumors; chemotherapy-resistant cell lines Dose-dependent growth inhibition and cell killing Sarafraz-Yazdi et al., Ann Clin Lab Sci 2015
Ovarian SKOV-3 and OVCAR-3 cell lines vs HUVEC (normal blood-vessel cells) Necrosis in cancer cells; no toxicity to HUVEC Thadi et al., Ann Clin Lab Sci 2020
Acute myeloid leukemia 3 cell lines Necrosis within 4 h Thadi et al., Anticancer Res 2020
Colon 6 cancer cell lines vs 1 normal colon cell line Necrosis of cancer cells, including stem-like CD44-positive cells Thadi et al., Anticancer Res 2021
Cervical SiHa cancer cell line vs normal cervical cells Cancer cells killed; normal cells not Krzesaj et al., Ann Clin Lab Sci 2025

Animal studies

The animal studies used transplanted tumor models, mostly in mice. We found no published safety or toxicology studies of PNC-27 in animals.

Model Reported finding Source
Human and mouse acute myeloid leukemia in transplanted mice Killed both bulk leukemia cells and leukemia stem cells; normal blood-forming stem cells were spared Wang et al., Leukemia 2020
Mouse ovarian cancer in the abdominal cavity Adding PNC-27 to weekly paclitaxel significantly reduced tumor growth compared with paclitaxel alone Alagkiozidis et al., Ann Clin Lab Sci 2017
Colon cancer tumors in live animals Necrosis of tumor nodules but not of normal tissue Thadi et al., Anticancer Res 2021

The best-known animal result, complete destruction of transplanted rat pancreatic tumors in nude mice (mice without a working immune system), was obtained with the sister peptide PNC-28, not PNC-27. The strongest effect was seen when the peptide was given into the same body cavity as the tumor (Michl et al., Int J Cancer 2006).

Human data

There are none. A search of ClinicalTrials.gov returned no registered studies of PNC-27 (ClinicalTrials.gov), and PubMed contains no human trial or case series. Federal prosecutors stated in 2020 that PNC-27 had not undergone clinical trials in humans in the United States to determine its efficacy, safety, or side effects (US Attorney’s Office, 2020).

Nothing is known about how PNC-27 behaves in the human body: whether it survives in the blood, reaches tumors, or harms normal tissue. No human pharmacokinetic or toxicology data have been published.

Limits of the evidence

  • One research network. Most PNC-27 papers come from the developers and their collaborators. Three of the authors of the 2022 pore study are inventors on patents for PNC-27 and PNC-28, and the first author is affiliated with NomoCan Pharmaceuticals (Sarafraz-Yazdi et al., Biomedicines 2022). The City of Hope leukemia study received its peptide from a company named Oncolyze (Wang et al., Leukemia 2020).
  • “No effect on normal cells” is not universal. The independent Chinese group found PNC-27 only 2–3 times more potent against tumor cells than against normal cells in culture (Yang et al., J Biol Chem 2010). That is a much narrower margin than “kills cancer cells but not normal cells” suggests.
  • Early-stage findings only. Killing cancer cells in a dish or in transplanted tumors in mice does not show whether a peptide can reach tumors in people, how long it lasts in the blood, or whether it is safe.

Regulatory status and enforcement

FDA warning (2017)

On January 10, 2017, the FDA warned consumers not to buy or use PNC-27 sold through a website as a treatment or cure for cancer (FDA, 2017). The FDA reported:

  • An FDA laboratory found the bacterium Variovorax paradoxus in a PNC-27 solution for inhalation.
  • On March 27, 2017, a second sample of the inhalation solution tested positive for a different bacterium, Ralstonia insidiosa.
  • The products were offered as a nebulized (inhaled) solution, intravenous solution, and vaginal or rectal suppositories.
  • The FDA has not evaluated or approved PNC-27 as safe and effective for any disease, including any cancer.
  • Contaminated products carry a risk of serious, potentially life-threatening infection, especially for people with weakened immune systems.

The FDA said it had not received reports of illness linked to the products at that time.

Federal criminal case (2020–2021)

In August 2020, a 28-count federal indictment charged a Birmingham, Alabama man with conspiracy and fraud over PNC-27 products (US Attorney’s Office, 2020). According to the indictment and the later plea agreement:

  • He bought the peptide from a Chinese manufacturer, paying more than $600,000 in 2015 and 2016, and repeatedly assured the supplier it was for laboratory research only.
  • He made homemade suppositories in his kitchen and in a rented warehouse. Neither was sterile, and the process did not follow good manufacturing practices.
  • Customers reported finding pieces of hair in their suppository packs (an allegation in the indictment).
  • The products were marketed as a cancer treatment to alternative-medicine doctors and patients in the US, and sold to a holistic cancer clinic operating in Mexico.
  • He presented the sales as a research effort and called himself a research director, though he had no formal medical training.

He pleaded guilty in January 2021 to conspiracy to fraudulently introduce adulterated and misbranded drugs into interstate commerce. On May 26, 2021, he was sentenced to 30 months in federal prison and three years of supervised release, and ordered to forfeit $900,000 (US Attorney’s Office, 2021). The plea agreement stated that he received millions of dollars from PNC-27 sales in 2015 and 2016.

Sports

PNC-27 is not named on the WADA Prohibited List. As a substance with no approval for human therapeutic use, it falls under class S0, non-approved substances, which are prohibited at all times (WADA 2026 Prohibited List).

Side effects and risks

No human safety data

No study has measured side effects, safe exposure levels or drug interactions of PNC-27 in people. Mouse studies reported little harm to normal blood-forming cells or normal tissue, but mouse findings cannot be used to predict human safety (Wang et al., Leukemia 2020).

Contamination and product quality

The two documented problems with products sold to patients are bacterial contamination of inhalation solutions found by FDA laboratories, and non-sterile kitchen manufacturing established in the federal case. Material sold as “research peptide” has no regulatory quality control, so its identity, purity and sterility cannot be assumed.

Delayed cancer treatment

PNC-27 has never been compared with standard cancer treatment, and nothing shows it can replace it. In its warning, the FDA advised patients with cancer to discuss treatment options with a licensed health care professional, and advised anyone who had used a PNC-27 product and has concerns to contact their health care provider (FDA, 2017).

Key takeaways

  • A lab-designed hybrid peptide. PNC-27 joins the HDM-2-binding stretch of p53 to the cell-penetrating peptide penetratin, and in the lab it kills cancer cells by punching pores in their membranes.
  • Evidence stops at mice. Results come from cell culture and mouse tumor models. No human trial has been published or registered.
  • Selectivity is less certain than claimed. The developers report no effect on normal cells, but an independent lab found only a 2–3-fold difference in potency between tumor and normal cells.
  • Regulators and prosecutors have acted. The FDA warned in 2017 that PNC-27 products contained bacteria, and an Alabama seller was sentenced in 2021 to 30 months in prison for making and selling PNC-27 suppositories as a cancer treatment.
  • Not a medicine. PNC-27 is not approved for any use, its handling in the human body is unknown, and it is prohibited in sport under WADA class S0.

Sources

  1. Kanovsky M, Raffo A, Drew L, et al. 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):12438–12443. PubMed.
  2. Do TN, Rosal RV, Drew L, et al. Preferential induction of necrosis in human breast cancer cells by a p53 peptide derived from the MDM2 binding site. Oncogene. 2003;22(10):1431–1444. PubMed.
  3. Rosal R, Pincus MR, Brandt-Rauf PW, et al. 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):1854–1861. PubMed.
  4. National Center for Biotechnology Information. PubChem Compound Summary for CID 16201774 (PNC-27). PubChem.
  5. Michl J, Scharf B, Schmidt A, 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. PubMed.
  6. 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. PubMed.
  7. Sarafraz-Yazdi E, Bowne WB, Adler 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. PubMed.
  8. Sookraj KA, Bowne WB, Adler V, et al. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer Chemother Pharmacol. 2010;66(2):325–331. PubMed.
  9. Yang H, Liu S, Cai H, et al. 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):25666–25676. PubMed.
  10. Davitt K, Babcock BD, Fenelus M, 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. PubMed.
  11. Sarafraz-Yazdi E, Gorelick C, Wagreich AR, 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. PubMed.
  12. Alagkiozidis I, Gorelick C, Shah T, 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. PubMed.
  13. 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. PubMed.
  14. Thadi A, Gleeson EM, Khalili M, 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. PubMed.
  15. 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. PubMed.
  16. Thadi A, Morano WF, Khalili M, 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. PubMed.
  17. 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. PubMed.
  18. 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. PubMed.
  19. 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. PubMed.
  20. Food and Drug Administration. FDA warns cancer patients not to use PNC-27 products for treatment. January 10, 2017; updated March 27, 2017. FDA (archived).
  21. US Attorney’s Office, Northern District of Alabama. Birmingham man indicted on conspiracy and fraud charges for making unapproved drug products in his kitchen and warehouse and marketing and selling them as a cancer treatment. August 26, 2020. justice.gov.
  22. US Attorney’s Office, Northern District of Alabama. Birmingham man sentenced for making unapproved drug products. May 26, 2021. justice.gov.
  23. ClinicalTrials.gov. Search results for “PNC-27” (no registered studies). Accessed October 2026. ClinicalTrials.gov.
  24. World Anti-Doping Agency. 2026 Prohibited List (S0 Non-approved substances). WADA.