PNC-27 is a synthetic 32-residue chimeric peptide built from residues 12–26 of the human tumour-suppressor protein p53 (the HDM-2/MDM2-binding domain) fused to a membrane-residency leader sequence of the cell-penetrating type.12 It is studied strictly as a research reagent for tumour-cell membrane biology and is sold for laboratory research use only. PNC-27 is not an approved drug: it has not been evaluated or approved by any regulator as safe or effective, no human clinical trials have been published, and the U.S. FDA has warned the public against using PNC-27 products marketed as cancer treatments.4 All findings below come from cell-culture and patient-derived ex-vivo systems, not from people. Several reported chemical and biological values were verified against PubChem and primary literature; where a value is not established, that is stated plainly rather than estimated.
Sequence & identity
Linear 32-residue peptide; identity (formula C₁₈₈H₂₉₃N₅₃O₄₄S, InChIKey MZCACYLMMMXSKC-KOCFKOPYSA-N) per PubChem CID 16201774.3
Mechanisms studied
Researchers reported that the p53-derived segment of PNC-27 adopts a three-dimensional conformation directly superimposable on the structure of the same p53 residues bound to HDM-2 (MDM2), indicating the peptide is configured to engage HDM-2.1 In cell models, the authors observed that PNC-27 binds HDM-2 that is aberrantly expressed on the outer plasma membrane of cancer cells, forming roughly 1:1 PNC-27–HDM-2 complexes that line trans-membrane pores; in MIA-PaCa-2 pancreatic carcinoma cells these pores were measured at an average inner diameter of about 34.5 ± 5.6 nm, and pore formation was reported to drive rapid tumour-cell lysis and necrosis.2 Investigators reported that untransformed cells, which do not display appreciable surface HDM-2, formed no pores and were not killed, attributing the observed selectivity to membrane HDM-2 expression.12
Dosing in the research literature
The figures below summarise regimens as reported in published research — they are not recommendations or directions for use.
| Source / model | Regimen reported | Notes |
|---|---|---|
| Sarafraz-Yazdi et al., Biomedicines 2022 (in-vitro)2 | Concentrations as reported in cell-culture experiments: ~100–150 µg/mL (≈25–37.5 µM); short 3–10 min exposures at 37°C induced pore formation, with reported ~100% tumour-cell killing (by LDH release) at concentrations above 100 µg/mL. | In-vitro cell-line values only. Not a dosing recommendation. No validated, safe human dose exists; PNC-27 is research-use-only and is not an approved therapy. |
| General | Not established for human use. | No published human clinical trials and no regulator-approved dosing. Any in-vivo/animal exposures in the literature are experimental and not transferable to humans. |
Effects observed in research
In cancer cell lines (including MIA-PaCa-2 pancreatic carcinoma, A2058 melanoma, and rat BMRPA1.TUC-3 pancreatic cancer), studies reported dose-dependent membrane pore formation followed by cell lysis and necrosis, while untransformed fibroblasts and normal pancreatic acinar cells showed no pore formation under the same conditions.2 In an ex-vivo study, investigators reported that PNC-27 was cytotoxic in a dose-dependent manner to freshly isolated patient-derived epithelial ovarian cancer cells (including a chemotherapy-resistant line), whereas the inactive control peptide PNC-29 had no effect; the authors noted this was the first demonstration on freshly isolated primary human cancer cells and was performed ex vivo, not in patients.5 These are laboratory observations in cells and tissue; no clinical effects in humans have been established.
Strength of evidence
Grade C — animal/in-vitro and ex-vivo data only. The evidence base for PNC-27 consists of structural modelling, cancer cell-line experiments, and ex-vivo work on patient-derived tumour cells.125 There are no published controlled human clinical trials, and the closely related peptide PNC-28 accounts for most in-vivo (mouse) reports. PNC-27 is not an approved drug; the U.S. FDA has stated it is not evaluated or approved and has cautioned against products marketing it as a cancer treatment.4 No CAS Registry Number is listed in PubChem for this peptide, and a validated human safety profile has not been established. Reported anticancer selectivity should be regarded as a preclinical hypothesis, not a demonstrated clinical effect.
Reconstitution & storage
Reconstitute with bacteriostatic water for laboratory handling. Store lyophilised material frozen and reconstituted material refrigerated. Use Peptigo’s reconstitution calculator and storage cheat sheet for working figures.
References
- 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 USA. 2010;107(5):1918-1923. doi:10.1073/pnas.0909364107. PMID:20080680.
- 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):945. doi:10.3390/biomedicines10050945. PMC9138867.
- PubChem Compound Summary, CID 16201774 (PNC-27). National Library of Medicine / NCBI. Molecular formula C188H293N53O44S; molecular weight ~4031.7 g/mol; InChIKey MZCACYLMMMXSKC-KOCFKOPYSA-N. https://pubchem.ncbi.nlm.nih.gov/compound/16201774 (accessed 2026-06-03).
- U.S. Food and Drug Administration. FDA warns against using PNC-27 for cancer treatment (safety alert, January 12, 2017): PNC-27 is not FDA-approved and the agency has not evaluated its safety or efficacy for any disease, including cancer; an FDA laboratory found Variovorax paradoxus bacterial contamination in a PNC-27 inhalation-solution sample. https://www.fda.gov/
- Sarafraz-Yazdi E, 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.