PNC-27 Protocol

Dosing & Research

Last Updated: September 4, 2026

Also known as: PNC27, Anti-Cancer Peptide PNC-27, p53-HDM-2 Binding Peptide, Chimeric p53-Penetratin Peptide

Chemical Identity

Amino Acid Sequence: PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG
Molecular Formula: C188H293N53O44S
Molecular Weight: 4031.7 g/mol
CAS Number: 1159861-00-3

Selective cytotoxicity in cancer cell lines, Membrane-localized HDM-2 (MDM2) targeting, Transmembrane pore formation ("poptosis") research, Mitochondrial membrane disruption studies, Preclinical solid tumor and AML xenograft models

Evidence Level

Preclinical Research Only

Species Studied

Human cell lines • Primary human tumor cells • Mouse xenograft models • Mouse aml models

Half-Life

Not Well Characterized In Vivo

Administration

• Injection
• Oral

Frequency

Varies by study protocol (e.g., daily IP dosing in AML models)

How It Works

Synthetic 32-amino acid chimeric peptide combining the HDM-2 (MDM2)-binding domain of p53 (residues 12-26) with a membrane-residency/penetratin-type sequence. Binds membrane-localized HDM-2, which is overexpressed on the surface of many cancer cells but largely absent from normal cells, and self-assembles into oligomeric transmembrane pores (visualized by immuno-electron microscopy). Pore formation triggers colloid-osmotic necrosis ("poptosis") rather than classical apoptosis, and also disrupts mitochondrial membranes in treated cancer cells. Activity is largely p53-independent, so it remains active in cells with disrupted nuclear p53 signaling.
Selective cytotoxicity in cancer cell lines
Membrane-localized HDM-2 (MDM2) targeting
Transmembrane pore formation ("poptosis") research
Mitochondrial membrane disruption studies

Dosing Structure

Dose

Preclinical research only

Frequency

Varies by study protocol (e.g., daily IP dosing in AML models)

Notes

Extensively studied in vitro and in mouse xenograft/AML models, with reported selectivity for HDM-2-expressing cancer cells over normal cells; no completed high-quality human Phase 2/3 clinical trials as of 2026. FDA has issued public warnings against unapproved products marketed online as cancer treatments, including contamination concerns in some unregistered preparations. Research and laboratory reference only -- not medical advice, and not a substitute for standard oncology care.

Example Protocols

Dose: Preclinical research only

Frequency: Varies by study protocol (e.g., daily IP dosing in AML models)

Duration: Preclinical study-dependent; no established human protocol

Off Period: Not listed

Calculate dosing →

Find Research Grade PNC-27

Recommended vendors for sourcing research-grade material. PeptaBase does not sell peptides directly.

Vendor One Research Labs

COA Verified

Third-party COA-verified research peptides with published batch testing.

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Vendor Two Sciences

Purity Tested

US-based research compound supplier with independent purity testing.

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Vendor Three Peptide Co.

Bulk research peptide sourcing with batch-level documentation.

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View all recommended vendors →

Protocol Notes

•

Extensively studied in vitro and in mouse xenograft/AML models, with reported selectivity for HDM-2-expressing cancer cells over normal cells; no completed high-quality human Phase 2/3 clinical trials as of 2026.

•

FDA has issued public warnings against unapproved products marketed online as cancer treatments, including contamination concerns in some unregistered preparations.

•

Research and laboratory reference only -- not medical advice, and not a substitute for standard oncology care.

What Is PNC-27?

PNC-27 is a synthetic 32-amino-acid chimeric peptide designed to selectively kill cancer cells. It fuses the HDM-2 (MDM2)-binding domain of the p53 tumor suppressor (residues 12-26) to a membrane-residency/penetratin-type sequence. In preclinical models it binds membrane-localized HDM-2 - a protein overexpressed on the surface of many cancer cells but largely absent from normal cells - and forms transmembrane pores that trigger rapid necrotic cell death, sometimes called 'poptosis,' while sparing normal cells. It is an active preclinical research compound with no completed high-quality human clinical trials as of 2026, and the FDA has warned against unapproved products marketed online as cancer treatments.

Research Observations - Not Medical Claims

▸Mechanism and selectivity (PNAS, 2010; PMID: 20080680): PNC-27 adopts an HDM-2-binding conformation directly superimposable on p53's own HDM-2-bound structure; the peptide binds membrane-associated HDM-2, which was detected at significant levels on a wide range of cancer cell lines but not on several untransformed cell lines, and untransformed cells engineered to express surface HDM-2 became susceptible to PNC-27.
▸Pore formation: Immuno-electron microscopy studies describe PNC-27/HDM-2 complexes oligomerizing into transmembrane pores in cancer cell membranes, consistent with colloid-osmotic necrosis rather than classical caspase-driven apoptosis.
▸AML research (Leukemia, 2020; PMID: 31337857): Membrane HDM-2 was preferentially expressed on acute myeloid leukemia (AML) cells, including leukemia-stem-cell-enriched subpopulations, but not on normal hematopoietic stem cells or acute lymphoblastic leukemia blasts; PNC-27 selectively killed AML cells in vitro and in vivo with minimal off-target hematopoietic toxicity.
▸Broad preclinical cytotoxicity: Selective activity has been reported across numerous cancer cell lines and primary tumor cells (including pancreatic, breast, ovarian, colon, cervical, lung, melanoma, AML, and CML models), with IC50 values typically in the low-to-mid micromolar range depending on cell type.
▸Mitochondrial disruption: In addition to plasma-membrane pore formation, PNC-27 has been reported to disrupt mitochondrial membranes in treated cancer cells.
▸p53-independence: Cytotoxic activity has been observed in models with disrupted nuclear p53 signaling, suggesting the mechanism does not require an intact p53 pathway.

Evidence Summary

Preclinical Research OnlySynthetic research peptide; ACTIVE preclinical status -- not FDA-approved for any indication. The FDA has issued public warnings against unapproved products marketed online as cancer cures. For research and laboratory reference only -- no medical claims.

Evidence StrengthPreliminary