library.onepin.app/pnc-27 Peptide Education Library
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OnePin Peptide Library · Immune

Immune Chimeric p53 / penetratin anti-cancer peptide Not FDA-approved · investigational

PNC-27

PNC27

Chimeric p53 / penetratin anti-cancer peptideHDM-2 (MDM2) membrane-binding peptideCancer-selective pore-forming peptide32-amino-acid cationic alpha-helical peptide

PNC-27 is a 32-amino-acid chimeric anti-cancer peptide developed by Drs. Matthew Pincus and Joseph Michl at SUNY Downstate Medical Center. It fuses residues 12-26 of the HDM-2 binding domain of the p53 tumor suppressor with a membrane-residency / penetratin-like leader (Antennapedia-derived). PNC-27 selectively kills cancer cells by binding HDM-2 (MDM2) overexpressed on the cancer cell plasma membrane, forming transmembrane pores that cause rapid necrotic cell death (a process termed 'poptosis'). Normal cells, which carry only low or undetectable surface HDM-2, are spared. Preclinical studies have demonstrated efficacy against pancreatic, breast, melanoma, leukemia, ovarian, cervical, and other cancers.

Quick Start
Route
IV (per published literature)
Start low
0.1-1 mg/kg per published preclinical protocols (REVIEW: human dosing not established)
Frequency
Daily during a research cycle
Timing
Not applicable for IV

Research dosing only. Not approved for clinical / human use. Pin alone in any reconstitution scenario - chemistry profile (cationic +6, Met / Trp residues, membrane-active) restricts mixing with most other peptides.

❋

Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first
Quick Start
Conservative start
0.1-1 mg/kg per published preclinical protocols (REVIEW: human dosing not established) · IV (per published literature) · Daily during a research cycle
Lowest starting point. Hold about a week to assess tolerance before stepping up.
0.1-1 mg/kg per published preclinical protocols (REVIEW: human dosing not established)
Daily during a research cycle
Expert
Targeted Tumor Necrosis
5-10 mg · SubQ · Daily
in vitro · Sarafraz-Yazdi et al. 2010 (Proc Natl Acad Sci U.S.A. 2010;107(5):1918-1923)
5-10 mg
Daily
Reconstitution CalculatorU-100
050100u
Draw to
— units
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01

How it works

PNC-27 contains residues 12-26 of the HDM-2 binding domain of p53 attached to a membrane-residency peptide (MRP) leader sequence that drives transport across cell membranes. Cancer cells express HDM-2 on their plasma membrane (normal cells do not). PNC-27 binds membrane HDM-2, then the cationic / amphipathic peptide inserts into the lipid bilayer and forms transmembrane pores. The pores cause rapid necrotic lysis of the cancer cell (poptosis). A 2024 study revealed a secondary mechanism: PNC-27 also enters cells and selectively disrupts mitochondrial membranes while sparing lysosomes, suggesting dual membrane-targeting activity.

PNC-27 contains residues 12-26 of the HDM-2 binding domain of p53 attached to a membrane-residency peptide (MRP) leader sequence that drives transport across cell membranes. Cancer cells express HDM-2 on their plasma membrane (normal cells do not). PNC-27 binds membrane HDM-2, then the cationic / amphipathic peptide inserts into the lipid bilayer and forms transmembrane pores. The pores cause rapid necrotic lysis of the cancer cell (poptosis). A 2024 study revealed a secondary mechanism: PNC-27 also enters cells and selectively disrupts mitochondrial membranes while sparing lysosomes, suggesting dual membrane-targeting activity.

02

What to expect

Early
Days 1–7

Preclinical animal models: tumor response measured over days to weeks of daily dosing.

Mid
Weeks 2–4

Sustained anti-tumor activity reported across cycles in animal cancer models.

Later
Weeks 4–12

REVIEW - long-term safety and pharmacokinetics in humans unknown.

03

Evidence

HumanNo published trials
AnimalPresent
In-vitroStrong
2022PNC-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 E, Bowne WB, Adler V, Sookraj KA, Wu V, Shteyler V, Patel H, Oxbury W, Brandt-Rauf P, Zenilman ME, Pincus MR, Michl J, Biomedicines (MDPI) ↗review
2010Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes · Sarafraz-Yazdi E, Bowne WB, Adler V, et al., Proceedings of the National Academy of Sciences (PNAS) ↗peer reviewed
04

The honest take

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Selectively kills cancer cells

Supported

Confirmed in extensive preclinical work. HDM-2 surface expression on cancer (vs. normal) cells provides the selectivity mechanism. Multi-source verified (PNAS 2010, MDPI 2022).

Spares normal cells
Supported

Confirmed in animal cancer models. Normal cell membranes lack surface HDM-2, so PNC-27 does not bind / lyse them.

Approved for human use
Not supported

FALSE. Per multi-source check (exploring-peptides.com, peptide-db.com, peptideinitiative.com): not approved for human use, no human clinical trials initiated as of 2025.

05

Interactions & stacking

What's safe to combine, and what belongs in a separate pin.

Safe & synergistic

REVIEWMixing data not in published literature. Inferred safe pairings would be cationic / neutral / non-Met-containing peptides (similar profile to LL-37). Authoritative compatibility list not available.

Keep separate

GHK-CuINFERRED: GHK-Cu copper transfer can oxidize Met-20 and the three Trp residues (12, 18, 26) of PNC-27, degrading the peptide. Mirror of LL-37 / GHK-Cu incompatibility. REVIEW - not on published data.
GlutathioneINFERRED: Free thiol in glutathione can react with the Met-20 sulfide of PNC-27 (oxidation / sulfoxide formation). Mirror of LL-37 / glutathione incompatibility. REVIEW.
Anionic peptides (BPC-157, TA-1, TB-500, FOXO4-DRI)INFERRED: Net cationic charge of +6 on PNC-27 will electrostatically sequester anionic peptides through charge interaction. Mirror of LL-37 / anionic peptide pattern. REVIEW.
CJC-1295 with DACINFERRED: DAC moiety contains a maleimide group reactive with nucleophiles. PNC-27 contains multiple lysine residues whose epsilon-amines could react with maleimide. REVIEW.
06

Side effects & safety

Commonly reported

  • Mild local irritation, redness, or discomfort at the injection site (per exploring-peptides.com)
  • Fatigue or mild flu-like symptoms (per exploring-peptides.com)

Less common & notes

  • Rare allergic reactions; potential inflammation or systemic effects from excessive dosing (per exploring-peptides.com).
  • REVIEW: side effect profile is sourced from research-vendor aggregations, NOT FDA / clinical trial data.
  • No human safety profile exists.
07

Pharmacokinetics

Illustrative plasma concentration · 24 h
Half-life
~30 minutes (per exploring-peptides.com); less than 24 hours (per peptide-db.com). Both indicate short biological half-life.
Peak · Tmax
REVIEW - tmax not specified on aggregated sources
Elimination
REVIEW - not specified
Activity
REVIEW - not specified. Plasma half-life is short but biological pore-forming activity may persist beyond clearance.

Storage. REVIEW: Storage protocol not specified on Pep-Pedia / vendor sites. Standard peptide-class assumption: lyophilized stable at -20C long-term, reconstituted with bacteriostatic water stable refrigerated (2-8C) for ~28 days, protect from light.

08

Regulatory status

Not approved for human use (per peptide-db.com). Research use only. WADA status: not specifically listed. No FDA approval. No human clinical trials initiated.

Put it to work

Calculate, log & track

Open PNC-27 straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.

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The guide & community

The complete PNC-27 walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

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