PNC-27
also known as p53-penetratin chimeric peptide, PNC-28
Synthetic 32-amino-acid anticancer peptide combining the HDM-2-binding domain of p53 (residues 12-26) with a cell-penetrating peptide sequence. Selectively induces necrosis in cancer cells via transmembrane pore formation after binding to membrane-associated HDM-2, sparing normal cells which express minimal membrane HDM-2. Pre-clinical studies demonstrate efficacy across solid tumors and hematologic malignancies.
At a glance
In vitro / Pre-clinical only
Primary target — Membrane-bound HDM-2 protein on cancer cell surface [sarafrazyazdi-2022][krzesaj-2024].
Pathway — PNC-27 binds to membrane HDM-2 1-109 domain → transmembrane pore formation → rapid necrosis (poptosis) [pincus-2024][krzesaj-2024].
Downstream effect — Immediate cell lysis and extrusion of intracellular contents; secondary mitochondrial membrane disruption [pincus-2024][krzesaj-2024].
Origin — Chimeric design: p53 transactivating domain (12-26) fused to penetratin CPP sequence [sarafrazyazdi-2022].
Feedback intact — N/A — cytotoxic mechanism, not signaling modulation.
| Parameter | Value |
|---|---|
| Clinical status | Pre-clinical only — no human trialsIn vitro and animal model data only. |
| In vitro concentrations | 10–100 μM rangeEffective concentrations in cell culture studies. |
| Shorter analogue | PNC-28 (28 AA variant)Retains HDM-2 binding and cytotoxic activity. |
| Evidence basis | Pre-clinical / In vitro |
Reconstitution
A pure mass-to-volume utility. Enter what you have in the vial; the atlas computes the volume per dose. No prescription information.
Not applicable — anticancer peptide, not metabolic
| Outcome | Finding |
|---|---|
| Fat loss mechanism | None — cytotoxic anticancer agent |
- — Human use — no clinical trials or safety data
- 01Pre-clinical status
PNC-27 has not been tested in human subjects. All data derive from in vitro cancer cell line studies and limited animal models. No approved clinical formulation, dosing protocol, or safety profile exists. [pincus-2024]
- 02Cell culture protocols
In vitro studies used 10–100 μM PNC-27 dissolved in cell culture medium. Peptide was added directly to cancer cell cultures (pancreatic, breast, colon, ovarian, leukemia lines) and incubated for 24–72 hours.
- 03Fluorescent labeling studies
Dual-labeled PNC-27 (green on N-terminus, red on C-terminus) demonstrated intact peptide binding to cancer cell membranes with combined yellow fluorescence at 30 minutes, persisting during cell lysis. [sookraj-2010]
- 04Membrane HDM-2 requirement
Cytotoxicity correlates directly with membrane HDM-2 expression levels. Blocking HDM-2's p53-binding domain (1-109) with monoclonal antibodies prevents PNC-27-induced necrosis.
Sources
of 41 rendered claims carry a resolvable citation.
- [krzesaj-2024]Krzesaj 2024 — Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes Causing Mitochondrial Disruption.
journal, 2024 - [pincus-2024]Pincus 2024 — Poptosis or Peptide-Induced Transmembrane Pore Formation: A Novel Way to Kill Cancer Cells without Affecting Normal Cells.
journal, 2024 - [sarafrazyazdi-2010]Sarafraz-Yazdi 2010 — Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes.
journal, 2010 - [sarafrazyazdi-2022]Sarafraz-Yazdi 2022 — PNC-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.
journal, 2022 - [sookraj-2010]Sookraj 2010 — The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide.
journal, 2010 - [thadi-2020]Thadi 2020 — Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells.
journal, 2020