PNC-28
Chimeric anticancer peptide containing p53 residues 17-26 fused to a penetratin leader sequence; kills cancer cells via necrotic membrane disruption.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | p53-penetratin chimeric peptide 28 |
| Category | Anticancer Peptide (Cancer Therapeutic) |
| Sequence | Penetratin leader + p53 residues 17-26 (ETFSDLWKLL); shorter HDM-2 binding domain than PNC-27 |
| Molecular Weight | ~3200 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); mg range intratumoral (animal) |
| 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-28 is a chimeric anticancer peptide structurally related to PNC-27 but containing a shorter p53-derived HDM-2-binding domain (residues 17-26 instead of 12-26). Like PNC-27, it is fused to a penetratin cell-penetrating peptide (CPP) leader sequence.
Key Structural Difference from PNC-27: PNC-28 contains a truncated HDM-2-binding domain (p53 residues 17-26, 10 amino acids) compared to PNC-27's longer domain (residues 12-26, 15 amino acids). This results in different HDM-2 binding characteristics and potentially different cancer cell line sensitivities (PMID: 35625682).
Mechanism of Killing:
- PNC-28 interacts with cancer cell membranes — the exact role of membrane-associated HDM-2 in PNC-28 binding is less clearly established than for PNC-27
- The penetratin leader sequence enables membrane insertion and pore formation
- Cancer cells undergo rapid necrotic death via membrane disruption
- LDH release confirms necrosis rather than apoptosis — proapoptotic markers (Bax, cytochrome c, caspase-3) are NOT elevated (PMID: 18931881)
- Normal cells are not affected at therapeutic concentrations
The critical mechanistic finding is that PNC-28 kills via necrosis, not apoptosis. This was demonstrated definitively by the absence of classical apoptotic markers and the presence of rapid membrane permeabilization (PMID: 18931881). This necrotic mechanism could bypass apoptosis resistance commonly seen in advanced cancers.
Relationship to PNC-27: Both peptides target cancer cells selectively and kill via membrane disruption, but PNC-28's shorter HDM-2-binding domain may alter target selectivity. PNC-28 has the distinction of being the first in the PNC peptide family to demonstrate in vivo antitumor activity (PMID: 16688716).
Key Research Areas
- Pancreatic Cancer — PNC-28 blocked PANC-1 pancreatic cancer growth in nude mouse xenograft model (PMID: 16688716) — the only in vivo data for any PNC peptide
- Necrotic Killing Mechanism — Detailed characterization showing necrosis via membrane disruption, not apoptosis (PMID: 18931881)
- Cancer Selectivity — Cytotoxic to cancer cells but not normal fibroblasts in vitro
- Structural Biology — Comparison with PNC-27 for HDM-2 binding domain optimization (PMID: 35625682)
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 0 | No clinical trials |
| Human observational | 0 | — |
| Animal in vivo | 1 | Nude mouse pancreatic cancer xenograft (PMID: 16688716) |
| In vitro | 1 | Mechanistic characterization (PMID: 18931881) |
| Systematic reviews | 0 | — |
Clinical Applications
- Cancer Adjunct Therapy — Preclinical anticancer agent; only PNC peptide with in vivo data
Protocols Using This Peptide
- No established clinical protocols. Research use only.
Ageless Peps Products
- APWS-PNC28-Vial — PNC-28 Vial, wholesale/clinical-label (draft)
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| Intratumoral (mouse) | mg range | Multiple injections | Weeks | PMID 16688716 |
| In vitro | 50-200 uM | Single exposure | 24-72 hours | PMID 18931881 |
Cycling
No cycling protocols established — preclinical stage only.
Contraindications & Safety
- Contraindications: Not established (preclinical compound)
- Common side effects: Not characterized in humans; no observable toxicity to normal tissues in animal study
- Drug interactions: Unknown; theoretical synergy with conventional chemotherapy
- Pregnancy/nursing: Not studied; contraindicated as research chemical
- Special populations: Not studied
Synergistic Combinations
- PNC-27 — Related peptide with longer HDM-2 binding domain; potentially complementary targeting profiles
- Conventional chemotherapy — Theoretical synergy with agents that upregulate HDM-2 membrane expression
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 16688716 | PNC-28 Blocks Pancreatic Cancer Growth In Vivo | 2007 | Animal in vivo |
| 18931881 | Penetratin Sequence Causes Tumor Necrosis Not Apoptosis | 2009 | In vitro |
References
- PMID 16688716 — In vivo pancreatic cancer xenograft study (J Surg Res 2007)
- PMID 18931881 — Necrosis vs. apoptosis mechanism characterization (Ann Surg Oncol 2009)
- PMID 35625682 — Comparative structural analysis with PNC-27 (Biomedicines 2022)
Related
Research Purposes Only. PNC-28 is a preclinical research compound. It has been tested in animal models but has not been tested in humans and is not approved for any clinical use.
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