PNC-27
Chimeric p53-Penetratin Anticancer Peptide | HDM-2 Targeting
$24
Daily dose
100-500mcg
Frequency
Once daily
Cycle length
8-12 weeks
Storage
-20°C (powder) / 2-8°C (reconstituted)
Key benefits
Selective anticancer peptide that kills cancer cells while sparing normal cells. Dual mechanism: membrane pore formation via HDM-2 binding and mitochondrial disruption. Demonstrated in vitro/ex vivo efficacy against pancreatic, breast, melanoma, leukemia, ovarian, and cervical cancers. Synergy with paclitaxel and ketone bodies documented.
How it works
Binds to HDM-2 (MDM2) overexpressed on cancer cell plasma membranes, forming oligomeric transmembrane pore complexes that cause rapid necrotic cell death ('poptosis'). Also enters cells via its MRP/CPP domain and disrupts mitochondrial membranes. Normal cells lack membrane HDM-2 and are unaffected regardless of p53 status.
Dosage protocols
Goal
Research Protocol
Dose
100-500mcg · Once daily
Route
Subcutaneous
Research indications
anticancer
Administration
Interactions
Safety notes
NOT FDA approved — explicit FDA warning issued against use
No verified human clinical trial data in peer-reviewed journals
No published human pharmacokinetic data
Contamination found in marketed products (FDA warning)
Should never replace FDA-approved cancer treatments
Discuss with oncologist before any consideration of use
Research studies
Landmark PNAS Study — HDM-2 Binding Conformation (2010)
MIA-PaCa-2, MCF-7, A-2058 cells | IC50 ~33 μM | 90 min to 100% kill
First major publication demonstrating PNC-27 adopts a p53-like structure when binding membrane HDM-2, forms transmembrane pores visualized by electron microscopy, and kills pancreatic, breast, and melanoma cancer cells while sparing normal fibroblasts.
View study →Intact Peptide Mechanism Study (2010)
Cancer cell lines | Structure-activity relationship | Covalent linkage required
Demonstrated PNC-27 remains intact during membranolysis. Neither the p53 domain alone, the MRP alone, nor both domains uncoupled could induce cancer cell death — the chimeric linkage is essential for activity.
View study →Leukemia Cell Selective Necrosis (2014)
K562, U937, HL60 cells | IC50 4.7-91.1 μM | No effect on normal lymphocytes
Extended PNC-27's selectivity to non-solid tumors. Killed K562 leukemia cells at nearly 100% while showing no cytotoxicity to normal murine lymphocytes at any tested concentration. Confirmed necrotic (not apoptotic) cell death.
View study →Ex Vivo Ovarian Cancer Efficacy (2015)
Patient-derived cells | Ovarian LD50 100 μg/mL | Paclitaxel synergy
First study using patient-derived (not cell line) cancer cells. Demonstrated dose-dependent killing of primary human ovarian and endometrial cancer tissue, with synergistic effects when combined with paclitaxel.
View study →Leukemia HDM-2 Targeting — Normal Cells Spared (2020)
Leukemia cells vs normal hematopoietic/stem cells | In vivo safety
Confirmed membrane HDM-2 targeting in leukemia cells with no effect on normal hematopoietic cells or umbilical cord stem cells. In vivo, PNC-peptide-treated animals showed no effects on blood cell differentials.
View study →Dual Mechanism: Mitochondrial Disruption Discovery (2024)
Cancer cells | Plasma membrane + mitochondrial targeting | Lysosome sparing
Revealed PNC-27 has a dual mechanism — beyond membrane pore formation, it enters cancer cells and directly disrupts mitochondrial membranes while leaving lysosomes unaffected. First evidence of organelle-specific targeting.
View study →Cervical Cancer + Ketone Body Synergy (2025)
HTB-35, SW756, HeLa cells | IC50 7-17 μM | Ketones reduce IC50 200-400%
Most recent publication demonstrating PNC-27 kills cervical cancer cells at some of the lowest IC50 values across any cancer type studied, with no effect on normal cervical epithelial cells. Ketone bodies (lithium acetoacetate, BHB) dramatically enhanced potency.
View study →