PNC-27

What is PNC-27?

PNC-27 was designed by Matthew Pincus, Josef Michl and colleagues at SUNY Downstate in Brooklyn from conformational analysis of p53’s MDM-2-binding domain. Its first 15 residues, PPLSQETFSDLWKLL, are p53 residues 12–26; the last 17, KKWKMRRNQFWVKVQRG, are a positively charged leader that sits in cell membranes. That leader is often described as penetratin, the Antennapedia-derived cell-penetrating peptide, but it is not the canonical penetratin sequence: it is that sequence reversed, with two isoleucine-to-valine changes and an added glycine.

The group’s work proposes that PNC-27 binds HDM-2 sitting in the plasma membrane of cancer cells and forms pores there, so the cells studied died by necrosis rather than apoptosis, and that this happened whether or not the cells had working p53. In their experiments, untransformed cell lines without membrane HDM-2 were not affected. A shorter analogue, PNC-28, carries p53 residues 17–26 with the same leader and was used in most of the animal work. All of this is cell and animal research; there are no clinical trials.

PNC-27 identity

Sources: Kanovsky M, et al., 2001, Rosal R, et al., 2004, UniProt and PubChem. PNC-27 has no FDA substance record and no CAS number confirmed by a registry; PubChem lists 1159861-00-3 only as a depositor synonym.

Certificates for the current lots

Each size is filled from its own lot and analysed separately by ILS Laboratories in San Diego, which states ISO/IEC 17025 accreditation for activities within its published scope. Both certificates are full QC panels: HPLC purity, net peptide content and identity by HPLC retention time, plus endotoxin, sterility, heavy metals and a fentanyl screen:

PNC-27 price

Price per vial and per milligram, read live from the store:

Published research on PNC-27

About two dozen papers, most of them from the originating group, all in cell lines, patient-derived cells in culture, or rodents.

• Design (2001). Three peptides from p53’s MDM-2-binding domain, each joined to the cationic leader, were tested on human cancer and normal cells in culture; the authors reported activity independent of p53 status. Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells. Kanovsky M, et al. PNAS, 2001.
• Necrosis, not apoptosis (2003). In breast cancer cell lines the p53(12-26) construct produced rapid non-apoptotic cell death. Do TN, et al. Oncogene, 2003.
• Structure (2004). Two-dimensional NMR of the 32-residue peptide showed three α-helical segments in an S shape. NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells. Rosal R, et al. Biochemistry, 2004.
• Membrane HDM-2 as the target (2010). The p53 part of PNC-27 matched the HDM-2-bound p53 structure, the peptide co-localised with HDM-2 in cancer-cell membranes, and untransformed cells became susceptible once made to express membrane-anchored HDM-2. Sarafraz-Yazdi E, et al. PNAS, 2010.
• The leader decides how cells die (2008). Using PNC-28, the p53 segment expressed alone gave apoptosis, while the same segment delivered as a peptide with the leader gave necrosis with membrane pores. Bowne WB, et al. Annals of Surgical Oncology, 2008.
• Independent work in leukaemia cells (2020). A City of Hope and Zhejiang University group reported membrane HDM2 on human and mouse AML blasts but not on normal haematopoietic stem cells, and studied the peptide in cell and mouse models. Targeting cell membrane HDM2: A novel therapeutic approach for acute myeloid leukemia. Wang H, et al. Leukemia, 2020.
• Imaging the pores (2022). Immuno-electron microscopy showed peptide and HDM-2 in roughly 1:1 ratios arranged in ring-like structures in cancer-cell membranes. Sarafraz-Yazdi E, et al. Biomedicines, 2022.

Several of the originating authors are named inventors on PNC-27 and PNC-28 patents, as their papers disclose. ClinicalTrials.gov lists no study of either peptide.

Regulatory status

PNC-27 is not an approved drug anywhere and is not in any FDA programme: it has no FDA application, no orphan designation, and has never been nominated for FDA’s compounding lists, so FDA has published no evaluation of it. Clean Peptide’s PNC-27 is a laboratory reference material only, not for human or veterinary use, and nothing on this page describes a treatment.

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