PNC-27
Chimeric anticancer peptide containing p53 residues 12-26 fused to a penetratin leader sequence; selectively kills cancer cells by targeting membrane-associated HDM-2.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | p53-penetratin chimeric peptide 27 |
| Category | Anticancer Peptide (Cancer Therapeutic) |
| Sequence | Penetratin leader + p53 residues 12-26 (PPLSQETFSDLWKLL); 32 amino acids total |
| Molecular Weight | ~3800 Da (estimated) |
| Molecular Formula | Not publicly disclosed |
| PubChem CID | N/A (research compound) |
| Administration | Intratumoral (research); systemic delivery under development |
| Typical Dose Range | Micromolar concentrations (in vitro); no clinical dosing established |
| Half-Life | Not characterized in humans |
| Storage | Lyophilized at -20C; reconstituted at 2-8C |
| FDA Status | Research-only — preclinical stage; no clinical trials registered |
| WADA Status | Not listed |
Mechanism of Action
PNC-27 is a rationally designed 32-residue chimeric peptide that exploits a fundamental difference between cancer and normal cells: the expression of HDM-2 (human double minute 2, also called MDM2) on the plasma membrane.
Structural Design: PNC-27 consists of two functional domains:
- p53 HDM-2-binding domain (residues 12-26 of p53) — This alpha-helical segment mimics the natural p53-MDM2 interaction interface, binding to HDM-2 with high affinity
- Penetratin leader sequence — A cell-penetrating peptide (CPP) derived from the Antennapedia homeodomain that enables membrane interaction and pore formation
Cancer Cell Selectivity: The key insight underlying PNC-27 is that cancer cells uniquely express HDM-2 on their plasma membranes, while normal cells sequester HDM-2 in the nucleus where it functions as a p53 negative regulator (PMID: 20080680). This membrane-associated HDM-2 provides a cancer-specific surface target.
Mechanism of Killing ("Poptosis"):
- PNC-27 adopts an alpha-helical conformation and binds to membrane-associated HDM-2 on cancer cell surfaces
- The penetratin domain inserts into the lipid bilayer
- Multiple PNC-27 molecules oligomerize at the membrane, forming transmembrane pores
- Rapid membrane disruption occurs, leading to cell lysis and necrotic death
- LDH release confirms necrotic (not apoptotic) cell death
This mechanism has been termed "poptosis" (peptide-induced transmembrane pore formation) and is fundamentally distinct from apoptosis-based cancer therapies (PMID: 35625682). Because many advanced cancers develop apoptosis resistance, a necrotic killing mechanism may bypass this resistance.
Key Research Areas
- Selective Cancer Cell Killing — Demonstrated cytotoxicity against breast (MDA-MB-468), pancreatic (PANC-1), melanoma (A375), leukemia (K562, HL60), ovarian, and cervical cancer lines while sparing normal cells (PMID: 20080680, 32878773, 40750238)
- Membrane HDM-2 Biology — Characterizing why cancer cells express HDM-2 on their membranes and how this relates to oncogenesis
- Hematologic Malignancies — PNC-27 kills leukemia cells (K562, HL60) but not normal hematopoietic cells (PMID: 32878773)
- Drug Delivery Enhancement — PNC-27 used as a targeting ligand for doxorubicin-loaded liposomes (Doxil), improving antitumor efficacy (PMID: 28565974)
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 0 | No clinical trials |
| Human observational | 0 | — |
| Animal in vivo | 0 | In vivo data via PNC-28 (related peptide) |
| In vitro | 3 | Multiple cancer cell lines tested |
| Systematic reviews | 0 | — |
Clinical Applications
- Cancer Adjunct Therapy — Preclinical anticancer agent targeting membrane HDM-2
Protocols Using This Peptide
- No established clinical protocols. Research use only.
Ageless Peps Products
- No Ageless Peps product currently available for PNC-27.
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| In vitro | 50-200 uM | Single exposure | 24-72 hours | PMID 20080680 |
Cycling
No cycling protocols established — preclinical stage only.
Contraindications & Safety
- Contraindications: Not established (preclinical compound)
- Common side effects: Not characterized in humans
- Drug interactions: Unknown; theoretical synergy with conventional chemotherapy
- Pregnancy/nursing: Not studied; contraindicated as research chemical
- Special populations: Not studied
Synergistic Combinations
- PNC-28 — Related peptide with overlapping but distinct HDM-2 binding profile; potential for complementary targeting
- Conventional chemotherapy — PNC-27-conjugated liposomal doxorubicin showed enhanced efficacy (PMID: 28565974)
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 20080680 | PNC-27 Kills Cancer Cells via Membrane HDM-2 Binding (PNAS) | 2010 | In vitro |
| 35625682 | Chimeric p53-Penetratin Peptide: Membrane-Pore Formation | 2022 | In vitro / Review |
| 32878773 | PNC-27 Induces Necrosis in Leukemia but Not Normal Cells | 2020 | In vitro |
References
- PMID 20080680 — Foundational PNAS paper: HDM-2 membrane binding and cancer cell selectivity
- PMID 35625682 — Structural characterization and poptosis mechanism (Biomedicines 2022)
- PMID 32878773 — Leukemia cell killing with normal hematopoietic cell sparing
- PMID 28565974 — PNC-27 as targeting ligand for Doxil (liposomal doxorubicin)
- PMID 20182728 — PNC-27 induces tumor cell lysis as intact peptide
- PMID 40750238 — PNC-27 kills cervical cancer cells but not normal cells (2025)
Related
Research Purposes Only. PNC-27 is a preclinical research compound. It has not been tested in humans and is not approved for any clinical use. All data is derived from in vitro cell culture studies.
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