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 IV
Frequency
Daily during a research cycle
Timing
Not applicable for IV
Starting dose. 0.1-1 mg/kg — Per published preclinical protocols (REVIEW: human dosing not established)
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.
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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
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
conservative starter
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)
Administered primarily in terminal or treatment-resistant contexts in the community. Highly experimental. No human trial has been conducted. The cited work is laboratory cell research, which cannot establish a human dose. This amount reflects community practice, not evidence.
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.
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
Each reference below was re-fetched from its PubMed record, and the quoted sentence was
confirmed to appear in that abstract and to support the claim it sits under. Follow any of
them to read the source.
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 plasma membrane and induces the formation of pores causing tumor cell lysis and necrosis.
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 plasma membrane and induces the formation of pores causing tumor cell lysis and necrosis.
Evidence scope. Cancer-cell mechanistic work; no established human IV dose, schedule, or safety.
Claims we could not support
No abstract we checked supports these for this molecule at this route. That is not the
same as saying they are false — it marks where the evidence is missing.
Dose/route: 0.1-1 mg/kg per published preclinical protocols (REVIEW: human dosing not established) via IV (per published literature), Daily during a research cycle. No checked live PubMed abstract supported this complete molecule/formulation/route/dose/frequency combination.
Primary safety claim: Mild local irritation, redness, or discomfort at the injection site (per exploring-peptides.com). No checked live abstract directly established this as the primary concern for the card's exact formulation and regimen.
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
Two different questions: what is documented about running these together, and what is documented about drawing them into the same syringe. A good pharmacological partner can still have to be pinned separately.
Documented together
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.
Check any specific pair in the Stack & Interaction Checker, which answers both questions separately. Absence of a documented conflict is not evidence of safety.
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 · 3.0 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
Bioavailability
REVIEW - not specified for the documented routes (IV / intratumoral / nebulized / suppository). IV bioavailability is by definition 100%.
Duration of action
REVIEW - not specified. Plasma half-life is short but biological pore-forming activity may persist beyond clearance.
Clearance
Likely peptidase-mediated metabolism in the liver and kidneys (per exploring-peptides.com).
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.
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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.