PNC-27

PNC-27 is a 32-residue chimeric p53-derived anticancer peptide that fuses the p53 residues 12–26 HDM-2-binding domain (PPLSQETFSDLWKLL) to a membrane-penetrating / membrane-residency sequence. It selectively binds HDM-2/MDM2 expressed on cancer-cell membranes, induces transmembrane pore formation, and causes necrotic lysis. No human clinical dataset was identified in the source material.

The core mechanism — consistent across primary papers — is that PNC-27 binds HDM-2/MDM2 expressed on the surface of cancer cells, adopts a p53-like binding conformation, and then induces transmembrane pore formation leading to necrotic cell lysis rather than classical apoptosis. The mechanism is reported to be selective for cancer cells expressing membrane HDM-2 and does not depend on endogenous wild-type p53 in the target tumor. Activity has been reported across breast cancer, leukemia, and epithelial ovarian cancer models, including ex vivo work on human primary ovarian cancer cells.