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Oncology & Specialized

PNC-27

Experimental peptide designed to punch holes in cancer cells that display HDM-2; preclinical only, and subject to an FDA consumer warning.

RestrictedEvidence level 1 of 5: Preclinical / anecdotalAlso: p53–HDM-2 membrane-targeting peptide, PNC-28 (related shorter analog)

Overview

PNC-27 was designed at SUNY Downstate by joining a piece of the tumor-suppressor protein p53 — the part that binds the cancer-associated protein HDM-2 (MDM2) — to a sequence that lets it insert into cell membranes. Many cancer cells display HDM-2 on their outer membrane, while normal cells generally do not. In laboratory studies, PNC-27 binds this surface HDM-2 and forms pores, causing cancer cells to burst while sparing normal cells. Effects have been seen across several cancer cell lines and in limited animal work. However, it has never completed a human clinical trial, and products sold directly to patients have been found contaminated. Cancer patients should pursue standard care and consider PNC-27 only within a formal trial.

Classification
Synthetic 32-amino-acid peptide: p53 HDM-2–binding domain fused to a membrane-penetrating sequence
Route
Intravenous or intraperitoneal (research only)
Half-life
Not well established

Mechanism of action

Primary targetMembrane-expressed HDM-2 (MDM2) on cancer cells
  1. Membrane HDM-2 recognitionp53-derived segment binds HDM-2 displayed on cancer cell surfaces.
  2. Membrane insertionPenetratin-like segment inserts into the lipid bilayer.
  3. Pore formationPeptide complexes assemble into transmembrane pores.
  4. Cell lysisPores cause rapid necrosis of the targeted cancer cell.
Downstream effects
  • Selective cancer-cell lysis (in vitro)
  • Tumor growth inhibition (animal)

Researched for

  • Pancreatic, breast and other solid tumor cell lines
  • Leukemia cell lines
  • Selective membranolytic cancer therapy concept

Research notes

  • Sarafraz-Yazdi, Pincus et al.: PNC-27 bound membrane HDM-2 and lysed multiple cancer cell lines while sparing normal cells in vitro.
  • Limited xenograft data suggest tumor growth inhibition; pharmacokinetics in humans are uncharacterized.
  • No completed or registered human efficacy trials.
  • FDA (2017) found Variovorax and Ralstonia bacteria in PNC-27 products sold to consumers and warned against their use.

Reported side effects

  • Unknown in humans
  • Theoretical off-target cell lysis
  • Infection risk from contaminated unregulated products
  • Infusion reactions

Contraindications & cautions

  • Use outside a clinical trial or supervised research protocol
  • Use as a substitute for standard cancer treatment
  • Pregnancy
  • Immunocompromise (infection risk from unregulated products)

Lab monitoring

  • Per oncology protocol and trial requirements
  • Staging workup and tumor markers per cancer type

Dosing and pricing for PNC-27

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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