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PNC-27
10mg · Single vial · Lyophilized powder
- Dose
- 10mg
- Pack size
- Single vial
- Form
- Lyophilized powder
- Storage
- 2–8°C
In vitro laboratory research use only · Not for human or veterinary use · Batch documented · Third-party tested · Ships from Canada
§ Research
Research · PNC-27
Overview
PNC-27 is a synthetic 32-residue chimeric sequence composed of residues 12-26 of the human p53 protein, comprising its HDM-2-binding domain, fused at the C-terminus to penetratin, a 17-residue membrane-translocating sequence derived from the Drosophila Antennapedia homeodomain. It was designed by researchers at SUNY Downstate Medical Center as an investigational anticancer agent. It serves as a research compound in studies of membrane-localized HDM-2, pore-forming cytotoxic sequences, and selective tumor cell lysis.
Mechanism of action
PNC-27 binds HDM-2 (human MDM2) expressed on the plasma membrane of many transformed cells, a localization reported to be largely absent from untransformed cells. Structural studies indicate the p53-derived segment adopts the same alpha-helical conformation that p53 assumes when bound to HDM-2. Binding of the intact molecule to membrane HDM-2 leads to formation of transmembrane pores, rapid loss of membrane integrity, and necrotic cell death rather than apoptosis, a process its developers have termed "poptosis." Mitochondrial membrane disruption has also been reported. The mechanism is described as independent of cellular p53 status, distinguishing it from small-molecule MDM2 antagonists that act by restoring p53 function.
Key research findings
- 01
In vitro studies across pancreatic, breast, ovarian, colon, cervical, and leukemia cell lines characterize HDM-2-dependent necrosis of transformed cells, with untransformed controls largely spared.
- 02
Ex vivo studies using primary epithelial ovarian cancer cells characterized cytotoxic effects, and combination studies with paclitaxel have been reported.
- 03
Nude mouse xenograft studies with the closely related PNC-28 characterized effects on pancreatic tumor growth.
- 04
No controlled clinical trials of PNC-27 have been published; the literature is confined to cell culture, ex vivo, and animal models.
Published references
Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells
Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer
The information above is derived from published preclinical and clinical research. It is provided for educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.