A p53-derived peptide that selectively disrupts cancer cell membranes while sparing normal tissue.
Contains the MDM-2 binding domain of p53 fused to an N-terminal leader sequence. Selectively targets HDM-2 protein overexpressed on tumour cell membranes (but absent on normal cell surfaces), inserting into the membrane and creating transmembrane pores that cause rapid cancer cell necrosis without affecting adjacent normal cells.
PNC-27 was developed by Matthew Pincus and colleagues and shows remarkable selectivity for cancer cells in vitro. Normal cells, which lack membrane-associated HDM-2, are unaffected even at high concentrations.
The mechanism of selective membrane disruption (as opposed to typical receptor-mediated drug action) represents a novel approach in oncology research. Studies span pancreatic, breast, melanoma, and leukemia cell lines.