PNC-27
An experimental anticancer peptide engineered to selectively disrupt cancer cell membranes that overexpress HDM-2 — preclinical research only.
A chimeric peptide combining a p53-derived HDM-2-binding sequence with a membrane-penetrating domain that induces necrotic cell death in cancer cells overexpressing HDM-2 at the plasma membrane, while sparing normal cells.
Mechanism of action
Selectively binds HDM-2 (the human MDM-2 homolog) expressed on the outer plasma membrane of cancer cells but not normal cells. Binding induces transmembrane pore formation and rapid necrotic cell death. The selectivity derives from the cancer-specific surface expression of HDM-2 — in normal cells, HDM-2 is intracellular and PNC-27 has minimal effect.
Primary uses
- Preclinical oncology research
- Solid tumor cell-line models
- Leukemia cell-line models
Typical dosing
No human dosing established. Community use carries unknown risk; not medical guidance.
Regulatory status
Not approved. Preclinical-stage investigational anticancer peptide. No completed clinical trials identified.
Status as of this entry's last review, October 4, 2026. Approvals, compounding rules and sport rules change; the regulatory tracker is checked more often.
What we checked
PNC-27 has a laboratory literature of about two dozen papers, almost all from one research group, and no human study. Its study cards are below; this section adds what can be checked around them.
Identity, computed
| Sequence | p53 residues 12-26 joined to a membrane-penetrating sequence (PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG) |
| Formula | C188H293N53O44S |
| Average mass | 4031.8 g/mol |
| Monoisotopic mass | 4029.204 Da |
| Isoelectric point | 11.78 (net charge +5.98 at pH 7) |
PNC-27 fuses the stretch of p53 that binds HDM-2 (residues 12-26, PPLSQETFSDLWKLL) to penetratin, a membrane-crossing segment from the Antennapedia homeodomain, as its 2022 title describes. The sequence is the one this entry's dataset gives; the calculator's free-acid mass above is for that sequence as written, because the peptide's C-terminal form was not stated in the abstracts we read.
Regulatory status, read October 5, 2026
Drugs@FDA: 0 records for “PNC-27”. EMA medicines list: 0 records for “PNC-27”. Run for semaglutide, the same queries return 6 and 5 records (and the registry search 84 trials), so a zero here is an absence, not a broken search. Not named on the WADA 2026 and 2027 Prohibited Lists. As a substance with no current approval for human therapeutic use, it falls under section S0 (non-approved substances), which is prohibited at all times; the lists were read on September 27, 2026.
What the maker or sellers claim
Claim, from research-chemical sellers: PNC-27 cures or treats cancer. It has never been given to a person in a published study.
What the wider literature shows
Beyond the cards below, the same group's 2024 review describes the mechanism it calls poptosis: PNC-27 and its shorter analogue PNC-28 bind HDM-2 sitting in cancer-cell membranes, form pores and burst the cell, sparing normal cells that carry little membrane HDM-2; it reports successful treatment of a metastatic pancreatic tumour and of human leukaemias in nude mice (Pincus et al., 2024). In two ovarian cancer cell lines, susceptibility tracked how much HDM-2 sat in the membrane (2020). A 2022 study attached PNC-27 to iron-oxide nanoparticles as a possible imaging agent.
What we looked for and did not find
No human trial, no registry record and no pharmacokinetic data. Independent replication outside the founding group is scarce, which the cards' sources also show.
| Source | Query | Results, October 5, 2026 | What it was |
|---|---|---|---|
| PubMed | PNC-27 | 25 | cell, mouse, modelling and nanoparticle studies |
| PubMed | PNC-28 HDM-2 | 4 | |
| ClinicalTrials.gov | PNC-27 | 0 | |
| Drugs@FDA (openFDA) | PNC-27 | 0 | |
| EMA medicines list | PNC-27 | 0 |
What the studies show
PNC-27 has been studied only in cells and tissue in the laboratory; no person has received it in a published study. The work comes largely from one research group, and it is described here as the abstracts state it.
In Vitro · 2010
How it finds cancer cells
PNC-27 joins residues 12-26 of p53, the stretch that binds HDM-2, to a membrane-penetrating sequence. Normal breast cells resisted it until they were engineered to display HDM-2 on their surface, after which they became susceptible, which the authors read as PNC-27 targeting membrane HDM-2 in cancer cells.
In Vitro · 2022
Pores in the membrane
Modelling and immuno-electron microscopy suggested that PNC-27 bound to HDM-2 lines pores in the cancer cell membrane; no pores formed in untransformed fibroblasts treated the same way.
In Vitro · 2020
Leukemia cell lines
In U937, OCI-AML3 and HL-60 leukemia cells, which carry HDM-2 in their membranes, PNC-27 caused necrosis and enzyme release within four hours, while normal blood-forming cells were spared.
In Vitro · 2024
Into the mitochondria
PNC-27 bound the p53-binding region of HDM-2 (residues 1-109), formed transmembrane pores, and also entered cancer cells and bound mitochondrial membranes, disrupting them.
In Vitro · 2025
Cervical cancer cells
PNC-27 killed cervical cancer cells but not normal cervical cells, which the authors tie to HDM-2 expressed only in the cancer cells' membranes.
References
- [pubmed] Michl J, et al. "PNC-27, a Peptide that Binds HDM-2 on the Cancer Cell Membrane, Induces Necrosis in Human Pancreatic and Colorectal Cancer Stem Cells." J Cell Biochem, 2021.
- [pubmed] Sarafraz-Yazdi E, 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):1918-23. PMID: 20080680.
- [pubmed] Sarafraz-Yazdi E, 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). PMID: 35625682.
- [pubmed] Thadi A, 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.
- [pubmed] Krzesaj P, 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.
- [pubmed] Krzesaj PK, 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.
- [pubmed] Pincus MR, et al. "Poptosis or Peptide-Induced Transmembrane Pore Formation: A Novel Way to Kill Cancer Cells without Affecting Normal Cells." Biomedicines, 2024;12(6). PMID: 38927351.
- [pubmed] Thadi A, 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.
Guides & tools
This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.