PNC-27
p53-penetratin chimeric peptide, PNC27
REC PPT-PNC-27 // REV 2026-10-04 // assessment changes are logged, never silent
A p53-derived peptide reported by one research group to lyse cancer cells; it has never been tested in a human trial, an independent laboratory measured its selectivity as roughly two- to three-fold rather than absolute, and a published case report describes a fatal haemorrhage in a patient who received it outside any trial.
What it is
A chimeric peptide joining residues 12 to 26 of the p53 transactivation domain, the region that binds HDM-2, to the penetratin cell-penetrating sequence from the Antennapedia homeodomain. The originating group proposes that it forms pores in the plasma membrane of cells displaying HDM-2 on their surface.
What it does
Studied in cultured cancer cell lines and in mouse xenografts, where the originating group reports membrane pore formation and necrosis said to depend on HDM-2 in the plasma membrane. It has never been studied in a registered human trial for any indication.
Does it work?
Europe PMC returns 65 records for the term, but most are unrelated papers that merely contain the string; roughly twenty concern the peptide, and nearly all of those share authors from one collaborating group in New York, concentrated in two journals. ClinicalTrials.gov holds no registered study, and the single record the count classifies as a randomised trial is a term collision rather than a PNC-27 trial. The central claim of absolute cancer selectivity has not been reproduced independently: working at West China Hospital, Sichuan University, Yang and colleagues reported in the Journal of Biological Chemistry in 2010 that PNC-27 killed tumour cells at concentrations only two to three times lower than in normal cells, and attributed even that modest margin to the penetratin carrier binding chondroitin sulfate rather than to HDM-2. The only human record in the literature is a 2017 American College of Gastroenterology case report describing massive gastrointestinal haemorrhage and death in a patient who had received experimental PNC-27 abroad, outside any trial. Nothing here supports any therapeutic use, and this record exists to mark the gap rather than to fill it.
Claims vs data
Each marketing claim, tagged by what the evidence actually supports.
| Binds HDM-2 and forms membrane pores in cancer cell lines in vitro | preclinical only |
| Reduces tumour size in mouse xenograft models | animal data only |
| Kills cancer cells only and leaves normal cells untouched | weak evidence |
| A selective cancer treatment for people | overreach |
Reference figures
Quoted from published reference material. These are not Peptuity recommendations.
molecular data — PubChem CID 16201774
The evidence, counted
Live counts from Europe PMC and ClinicalTrials.gov.
65 publications indexed, but only 1 randomised controlled trials and 0 registered interventional studies. Human evidence exists but is thin.
SRC // EUROPE PMC + CTGOV // "PNC-27" // FETCHED 2026-10-04 // 65 RECORDS
Most-cited literature
-
[01]
Evaluation of the use of therapeutic peptides for cancer treatment
Marqus S, Pirogova E, Piva TJ. · J Biomed Sci 2017 · 364 citations · DOI 10.1186/s12929-017-0328-x
-
[02]
Micropeptide CIP2A-BP encoded by LINC00665 inhibits triple-negative breast cancer progression
Guo B, Wu S, Zhu X, Zhang L, Deng J, Li F, Wang Y, Zhang S, Wu R, Lu J · EMBO J 2020 · 219 citations · DOI 10.15252/embj.2019102190
-
[03]
PAM50 assay and the three-gene model for identifying the major and clinically relevant molecular subtypes of breast cancer
Prat A, Parker JS, Fan C, Perou CM. · Breast Cancer Res Treat 2012 · 146 citations · DOI 10.1007/s10549-012-2143-0
-
[04]
The role of cell-penetrating peptides in potential anti-cancer therapy
Zhou M, Zou X, Cheng K, Zhong S, Su Y, Wu T, Tao Y, Cong L, Yan B, Jia · Clin Transl Med 2022 · 110 citations · DOI 10.1002/ctm2.822
Regulatory status
Formal, dated regulatory actions.
WADA — Prohibited List 2026
Prohibited in sport — WADA S0 (substance without any health-authority approval)
Common questions
Has PNC-27 been tested in people?
No. ClinicalTrials.gov holds no registered study of PNC-27 for any indication, and Europe PMC contains no clinical trial of it. The only human appearance in the literature is a 2017 American College of Gastroenterology case report of massive gastrointestinal haemorrhage and death in a patient who had received it experimentally abroad, outside any trial. It is not approved by the FDA, the Saudi FDA or any other regulator.
Has any independent laboratory replicated the selective-killing result?
Not as published. Almost every positive PNC-27 paper shares authors from a single collaborating group, and much of it appears in two journals. The clearest independent measurement points the other way: Yang and colleagues, at West China Hospital, Sichuan University, reported in the Journal of Biological Chemistry in 2010 that PNC-27 was cytotoxic to tumour cells at concentrations only two to three times lower than in normal cells, and that this modest margin tracked with chondroitin sulfate binding by the penetratin carrier rather than with HDM-2.
Is HDM-2 really present in the cell membrane?
That is the disputed premise of the whole model. HDM-2, the human form of MDM2, is conventionally described as a nuclear and cytoplasmic E3 ubiquitin ligase that regulates p53. Surface display of HDM-2 on cancer cells is central to the originating group's explanation and has not been independently established, which is why the mechanism remains contested rather than settled.
Why is a compound with this little evidence listed at all?
Because it circulates with claims attached to it, and a reader who meets those claims needs somewhere to read the actual state of the literature. Nothing on this page should be read as describing a treatment. Cancer care decisions belong with a treating physician, and a compound with no trial, a contested mechanism and a published fatal complication is not a therapeutic option.
Related compounds
FOXO4-DRI
Experimental senolytic. Mouse data only — genuinely frontier, genuinely unproven.
P21
Experimental neurogenic peptide. Preclinical only.
Epitalon
Soviet-era longevity peptide. Claims far exceed independently replicated evidence.
Dihexa
An angiotensin IV analog studied only in animals, whose two foundational mechanism papers were retracted in 2025 after a university investigation found falsified or fabricated data, and whose famous potency figure originated in a university press release rather than a cognition study.