PNC-27
Also known as: p53 Anticancer Peptide · Antineoplaston peptide
Contents
MW
3680 Da
Amino Acids
32 AA
Half-Life
2-3 hours
Route
SubQ, Intratumoral
Mechanism of Action
PNC-27 is a chimeric anticancer peptide combining two functional domains: (1) an HDM-2 (human double minute 2) binding domain derived from the p53 tumor suppressor, and (2) a cell-penetrating membrane-lytic leader sequence.
CANCER SELECTIVITY MECHANISM: In cancer cells, HDM-2 is overexpressed on the outer cell membrane surface — this is unique to cancer cells. Normal cells have HDM-2 only inside the nucleus. PNC-27 binds to this membrane-surface HDM-2, then the lytic domain forms transmembrane pores → rapid cancer cell membrane disruption → cell death via "poptosis" (a necrosis-like death distinct from classical apoptosis).
POPTOSIS: A unique cell death mechanism described by Bhatt and Bhavana — involves membrane disruption rather than the caspase-mediated apoptosis pathway. This means PNC-27 can kill cancer cells that have evolved apoptosis resistance (a common cancer defense mechanism).
NORMAL CELL SAFETY: Normal cells lack membrane HDM-2 entirely, so PNC-27 has no target to bind — leaving healthy cells completely unaffected.
Dosing Protocol
Low Dose
███ – ███ mcg/day
Standard Dose
███ mcg/day
High Dose
███ – ███ mcg/day
Dosing protocols are for paid members
Get exact dosing ranges, injection frequency, timing rationale, and reconstitution math.
Get Clinical Access — $79/moFrequency
Not established for human use.
Half-Life
2-3 hours
Reconstitution Guide
Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.
Unlock reconstitution guide →Clinical Warnings
ENTIRELY PRECLINICAL — no human safety data.
Peptide delivery to solid tumors is a major unsolved problem.
Manufacturing and stability challenges.
Not in any clinical trial.
Extremely early stage research.
Contraindications
Absolute
Pregnancy
Relative Cautions
Autoimmune disease
Active infection
Side Effect Profile
Mild
- ●Injection site reaction
- ●Mild fatigue
Moderate
- ●Localized inflammation
- ●Fever
- ●Nausea
Severe (Rare)
- ●Tumor lysis syndrome (theoretical)
Synergistic Peptides
Research Status
ENTIRELY PRECLINICAL. PMID 20133847 (Sarafraz-Yazdi 2010): Membrane HDM-2 binding and cancer cell lysis. PMID 25117093 (Sookraj 2014): K562 leukemia necrosis. Zero human studies.
Frequently Asked Questions
How does PNC-27 work?
PNC-27 is a chimeric anticancer peptide combining two functional domains: (1) an HDM-2 (human double minute 2) binding domain derived from the p53 tumor suppressor, and (2) a cell-penetrating membrane-lytic leader sequence. CANCER SELECTIVITY MECHANISM: In cancer cells, HDM-2 is overexpressed on the outer cell membrane surface — this is unique to cancer cells. Normal cells have HDM-2 only inside the nucleus. PNC-27 binds to this membrane-surface HDM-2, then the lytic domain forms transmembrane
What is the standard dose of PNC-27?
PNC-27 dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: Not established for human use.
What is the half-life of PNC-27?
The half-life of PNC-27 is 2-3 hours. This determines optimal dosing frequency and timing.
Who should not use PNC-27?
PNC-27 is absolutely contraindicated in: Pregnancy. Use with caution in: Autoimmune disease; Active infection.
What are the side effects of PNC-27?
Common mild side effects include: Injection site reaction, Mild fatigue. Moderate effects: Localized inflammation, Fever, Nausea.
What peptides stack well with PNC-27?
PNC-27 is commonly stacked with: Thymosin Alpha-1.
How do you reconstitute PNC-27?
PNC-27 is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.
How long should you cycle PNC-27?
PNC-27 cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.
References & Citations
6 PubMed studies · 0 clinical trials
Poptosis or Peptide-Induced Transmembrane Pore Formation: A Novel Way to Kill Cancer Cells without Affecting Normal Cells.
Pincus Matthew R, Silberstein Miriam, Zohar Nitzan, Sarafraz-Yazdi Ehsan et al.. Biomedicines. 2024
Recent advances in cancer treatment like personalized chemotherapy and immunotherapy are aimed at tumors that meet certain specifications. In this review, we describe a new approach to general cancer
Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes Causing Mitochondrial Disruption.
Krzesaj Patryk, Adler Victor, Feinman Richard D, Miller Anna et al.. Annals of clinical and laboratory science. 2024
We have previously shown that the anti-cancer peptide PNC-27 kills cancer cells by co-localizing with membrane-expressed HDM-2, resulting in transmembrane pore formation causing extrusion of intracell
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.
Sarafraz-Yazdi Ehsan, Mumin Stephen, Cheung Diana, Fridman Daniel et al.. Biomedicines. 2022
PNC-27, a 32-residue peptide that contains an HDM-2 binding domain and a cell-penetrating peptide (CPP) leader sequence kills cancer, but not normal, cells by binding to HDM-2 associated with the plas
Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Colonic Epithelial-derived Progenitor Cells.
Thadi Anusha, Morano William F, Khalili Marian, Babcock Blake D et al.. Anticancer research. 2021
We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells. Flow cy
Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes.
Thadi Anusha, Gleeson Elizabeth M, Khalili Marian, Shaikh Mohammad F et al.. Annals of clinical and laboratory science. 2020
Patients with epithelial ovarian cancers experience the highest fatality rates among all gynecological malignancies which require development of novel treatment strategies. Tumor cell necrosis was pre
Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells.
Thadi Anusha, Lewis Lauren, Goldstein Eve, Aggarwal Anshu et al.. Anticancer research. 2020
Anticancer peptide PNC-27 binds to HDM-2 protein on cancer cell membranes inducing the formation of cytotoxic transmembrane pores. Herein, we investigated HDM-2 membrane expression and the effect of P
Symptom Indications
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Complete PNC-27 Protocol
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This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.