PNC-27
PNC-27, a peptide. A chimeric peptide joining the p53 HDM-2-binding domain to a membrane-residency sequence, killing by membranolysis rather than by restoring p53…
A chimeric peptide joining the p53 HDM-2-binding domain to a membrane-residency sequence, killing by membranolysis rather than by restoring p53 transcription. PMID:14967026 verbatim: "we have performed two-dimensional NMR on a 32-residue sequence called PNC-27", which "forms amphipathic structures such that its hydrophobic residues coalesce on one face while the polar residues aggregate on the opposite face". PMID:32878773 verbatim gives the mechanism and the selectivity basis: "Anticancer peptide PNC-27 binds to HDM-2 protein on cancer cell membranes inducing the formation of cytotoxic transmembrane pores", acting "to induce cell necrosis and LDH release within 4 h". Selectivity is attributed to membrane HDM-2 being displayed on cancer but not normal cells (PMID:40750238). NOTHING HERE IS EXPRESSIBLE AS A HILL OCCUPANCY ROW: the target is a membrane-displayed protein and the effect is pore formation, not graded receptor activation.
PubChem CID 16201774 (C188H293N53O44S, 4032), CAS 1159861-00-3, re-queried 2026-09-26. The hit is name-specific — the synonym list is just "PNC-27" and the CAS — and 4032 Da is consistent with the 32-residue length PMID:14967026 states, which is the cross-check that makes the mass safe to store. NO HUMAN EXPOSURE, CONFIRMED BY TARGETED SEARCH: `PNC-27 AND (clinical OR patients OR phase)` returns 5 records, every one in vitro or ex vivo. The closest is PMID:26663795, whose title says "Patient-Derived Epithelial Ovarian Cancer" and whose own conclusion is "the efficacy of PNC-27 on freshly isolated, primary human cancer cells" — PATIENT-DERIVED CELLS, NOT PATIENTS, and it must not be read as a trial. The 2025 paper still writes in the conditional ("PNC-27 may be an effective drug against this cancer") 21 years after the 2004 structure paper, and the total indexed corpus is 25 records. THE RESIDUE SEQUENCE IS NOT IN ANY ABSTRACT READ — only "32-residue" and the domain description — so it is not recorded. PMID:21728981 is a REVIEW and is not cited here for any value. THE ONE POTENCY FIGURE IS A CONCENTRATION, NOT A DOSE, and is not stored as one: "PNC-27 is cytotoxic even at low doses (IC50=12.4 microM) to the human HTB-35 cervical cancer squamous epithelial cell line but not to a counterpart normal human PCS-480 cell line" (PMID:40750238).
Sources: PMID:14967026, PMID:32878773, PMID:40750238, PMID:28667027, PMID:26663795