PNC-27 – 5MG

What Is PNC-27?

PNC-27 is a 32-amino acid peptide that has been studied for its potential to mitigate the activity and proliferation of cancer cells. It is derived from p53, a protein involved in tumor suppression, and contains p53 residues 12–26 (the HDM-2-binding domain) joined to a cell-penetrating peptide, penetratin. PNC-27 has been suggested to induce cell death via necrosis in various cancer cell lines, including pancreatic cancer, ovarian cancer, and leukemia, among others.

Researchers speculate that the PNC-27 peptide may specifically target cancer cells while not appearing to interact with other cells. Initially synthesized in 2000 as a part of a research project associated with immunodeficiency, specifically HIV, this peptide was reported to exhibit the ability to bind with the double minute (HDM2) protein, which is deemed overly expressed on the membranes of the carcinogenic cells. Interestingly, PNC-27 does not appear to induce apoptosis, a common pathway for many anticancer research chemicals, but rather may act upon the cells via inducing necrosis. This mode of action suggests a direct, physical disruption of the plasma membrane, possibly mediated by the formation of pores that compromise cell integrity, leading to necrosis. More specifically, binding with this protein appears to perforate the membrane of cancer cells by forming holes and causing membranolysis. This allows for the influx of ions and the efflux of cellular contents, ultimately leading to cell death.⁽¹⁾

 

Specifications⁽¹⁾

Name	PNC-27
Structure	p53 residues 12–26 (the HDM-2-binding domain) joined to a membrane residency (cell-penetrating) peptide, penetratin
Sequence	Pro-Pro-Leu-Ser-Gln-Glu-Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu-Lys-Lys-Trp-Lys-Met-Arg-Arg-Asn-Gln-Phe-Trp-Val-Lys-Val-Gln-Arg-Gly (32 amino acids)
Molecular formula	C188H293N53O44S
Molecular weight	4031.7 g/mol
CAS number	1159861-00-3
Synthesis	Solid-phase peptide synthesis, US
Form	Lyophilized powder
Amount per vial	5 mg
Purity	98.33% (HPLC)
Storage	−20 °C, dry, protected from light
SKU	PNC-27

 

What Does Research Show About PNC-27?

How Does PNC-27 Select Cancer Cells?

Key finding: Conformational energy calculations suggested 1:1 complexes between PNC-27 and HDM-2, and immuno-electron microscopy found the two in about 1:1 ratios in ring-shaped structures in pores near the cancer cell surface; no pores formed in untransformed fibroblasts exposed to PNC-27.⁽²⁾

In 2009, a study aimed to evaluate whether the PNC-27 peptide may interact (and potentially induce necrosis) within non-cancerous cells. The researchers at the time believed that, based on the peptide structure, it might be able to bind with HDM-2 protein and interact singly with cancerous cells. HDM-2 protein is reportedly only present in cancerous cells. The study suggests that forming a 1:1 complex between PNC-27 and HDM-2 might be a key event in initiating the potential formation of transmembrane pores. The study employed theoretical and experimental approaches to understand the pore formation’s interaction and structural basis. Conformational energy calculations indicated that PNC-27 might form stable complexes with HDM-2, possibly aligning the leader sequence to not interfere with the core interaction. Yet, it did appear to participate in the pore structure. Immuno-electron microscopy gave researchers visual data of these complexes at the cancer cell surface, with observed ring-shaped structures at the pore sites, which they speculated may contain PNC-27 bound to HDM-2. Importantly, these pore structures were not observed in normal cells exposed to PNC-27, underscoring the peptide’s potentially selective toxicity towards cancer cells. Further, for this study, normal cells were implanted with HDM-2 protein. The PNC-27 peptide, which otherwise might not affect the cells, now showed affinity towards the modified cells.⁽²⁾

Does PNC-27 Act as the Intact Peptide?

Key finding: PNC-27 labeled with a green tag at one end and a red tag at the other gave punctate yellow fluorescence in the membranes of MCF-7 breast cancer cells within 30 minutes, showing the intact peptide at work during cell lysis, while untransformed MCF-10-2A cells remained viable.⁽³⁾

Another study⁽³⁾ conducted in 2010 aimed at understanding whether fragments of the peptide or the entire peptide might impact the formation of membrane pores. The hypothesis was that if the peptide remained intact, it might more effectively induce the membranolytic activity necessary for killing cancer cells. For this study, the peptide was induced with a green fluorescence chemical to the terminal containing an amino group and a red fluorescence chemical to the terminal containing the carboxyl group. This labeling strategy was crucial as it allowed the researchers to visually track the integrity of the peptide within the cellular environment. The breast tumor and control cells were then exposed to the modified peptide to see which color appeared on the membrane during membranolysis. Half an hour after the peptide, a bright yellow luminescence was reported upon membrane lysis, suggesting that the peptide was fully intact during this cellular membrane-killing process. This observation was critical as it suggested that the peptide’s structure was preserved during the interaction with the cell membrane, which would be essential for any cytotoxic activity. As expected, this was only seen in the cancerous cells while the control cells remained viable. The study’s researchers suggest that the intact form of PNC-27 may be crucial for its activity, as the peptide appears to selectively induce pore formation in cancer cell membranes—a process associated with the release of lactate dehydrogenase (LDH), a marker of cell lysis. The interaction of PNC-27 with cancer cell membranes was suggested to increase over time, correlating with increased LDH release and cell death. Kelley A. Sookraj et al. stated, “...by acting as the whole peptide, not fragments” and “results in initial uniform fluorescence … after which the peptide is degraded”.⁽³⁾

What Does Research Suggest About Leukemia Cells?

Key finding: In the p53-null K562 leukemia cell line, which expresses HDM-2 in its cell membranes, PNC-27 co-localized with HDM-2 and killed nearly 100% of the cells with LDH release, but had no effect on control leukocytes.⁽⁴⁾

In 2014, another study⁽⁴⁾ was initiated to determine the potential of the PNC-27 peptide on non-solid tissue tumor cells. As mentioned in the study, the purpose was “twofold: to investigate if these cells likewise express HDM-2 in their plasma membranes and to determine if our anti-cancer peptide induces tumor cell necrosis in these non-solid tissue tumor cells in a manner that depends on the interaction between the peptide and membrane-bound HDM-2.”⁽⁴⁾

The non-solid tumor cells were exposed to PNC-27, and the action examined. As part of the control, murine leukocyte cells were used. Upon fluorescence microscopy analysis, it was suggested that the HDM-2 protein was expressed in the non-solid tissue tumor cells and that the PNC-27 peptide appeared to exhibit potential selectivity towards these cells. Researcher Katlin Davitt et al. stated:

“… We conclude that the association of PNC-27 with HDM-2 in the cancer cell membrane [may] result in trans-membrane pore formation, which results in cancer cell death, as previously discovered in a number of different solid tissue tumor cells. Since K562 cells lack p53 expression, these effects of PNC-27 on this leukemia cell line [may] occur by a p53-independent pathway.” ⁽⁴⁾

What Do Studies in Other Cancer Cell Lines Suggest?

Key finding: In the acute myelogenous leukemia cell lines U937, OCI-AML3 and HL-60, HDM-2 was expressed at high levels in the cell membranes, and PNC-27 bound to it and induced cell necrosis and LDH release within 4 hours.⁽⁶⁾

A study⁽⁵⁾ was conducted on the peptide PNC-28, which is structurally and functionally very similar to the PNC-27 peptide. Both peptides are derived from p53 and appear to act only on the HDM-2 proteins in cancerous cells. In this study, PNC-28 (p53 residues 17–26 joined to penetratin) was tested on pancreatic cancer cells (MiaPaCa-2), where it caused necrosis through membrane pores. They suggested that PNC-28 appeared to inhibit the growth of cancer cells.

In a 2020 study,⁽⁶⁾ an experiment was conducted to determine the PNC-27 peptide potential on non-stem cells from the leukemia cell lines. Researchers reported the study focused on “acute myelogenous leukemia cell lines: U937, acute monocytic leukemia; OCI-AML3, acute myelomonocytic leukemia and HL60, acute promyelocytic leukemia.” These particular cell lines were selected due to their distinct phenotypic and genotypic characteristics, which might shed light on the peptide’s varying potential across different cancer cell types. After peptide exposure, it was observed that the HDM-2 protein appeared to be highly expressed in all leukemia cells, which were all targeted by the PNC-27 peptide.⁽⁶⁾

 

Certificate of Analysis

Batch / lot	C74166
Test date	8/21/2026
Testing laboratory	Vanguard Laboratory
Method	HPLC-UV/VIS (identity and purity)
Purity result	98.33%
Full report	Download the PNC-27 COA (PDF)

PNC-27 peptide is available for research and laboratory purposes only. We offer free shipping in the US for orders over $200. Please review our Terms and Conditions before ordering.

 

Frequently Asked Questions

 

References:

1. Davitt, K., Babcock, B. D., Fenelus, M., Poon, C. K., Sarkar, A., Trivigno, V., Zolkind, P. A., Matthew, S. M., Grin’kina, N., Orynbayeva, Z., Shaikh, M. F., Adler, V., Michl, J., Sarafraz-Yazdi, E., Pincus, M. R., & Bowne, W. B. (2014). The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells. Annals of clinical and laboratory science, 44(3), 241–248. https://pubmed.ncbi.nlm.nih.gov/25117093/
2. Sarafraz-Yazdi, E., Mumin, S., Cheung, D., Fridman, D., Lin, B., Wong, L., Rosal, R., Rudolph, R., Frenkel, M., Thadi, A., Morano, W. F., Bowne, W. B., Pincus, M. R., & Michl, J. (2022). PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis. Biomedicines, 10(5), 945. https://doi.org/10.3390/biomedicines10050945
3. Sookraj, K. A., Bowne, W. B., Adler, V., Sarafraz-Yazdi, E., Michl, J., & Pincus, M. R. (2010). The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer chemotherapy and pharmacology, 66(2), 325–331. https://doi.org/10.1007/s00280-009-1166-7
4. Davitt, K., Babcock, B. D., Fenelus, M., Poon, C. K., Sarkar, A., Trivigno, V., Zolkind, P. A., Matthew, S. M., Grin’kina, N., Orynbayeva, Z., Shaikh, M. F., Adler, V., Michl, J., Sarafraz-Yazdi, E., Pincus, M. R., & Bowne, W. B. (2014). The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells. Annals of clinical and laboratory science, 44(3), 241–248. https://pubmed.ncbi.nlm.nih.gov/25117093/
5. Bowne, W. B., Sookraj, K. A., Vishnevetsky, M., Adler, V., Sarafraz-Yazdi, E., Lou, S., Koenke, J., Shteyler, V., Ikram, K., Harding, M., Bluth, M. H., Ng, M., Brandt-Rauf, P. W., Hannan, R., Bradu, S., Zenilman, M. E., Michl, J., & Pincus, M. R. (2008). The penetratin sequence in the anticancer PNC-28 peptide causes tumor cell necrosis rather than apoptosis of human pancreatic cancer cells. Annals of surgical oncology, 15(12), 3588–3600. https://doi.org/10.1245/s10434-008-0147-0
6. Thadi, A., Lewis, L., Goldstein, E., Aggarwal, A., Khalili, M., Steele, L., Polyak, B., Seydafkan, S., Bluth, M. H., Ward, K. A., Styler, M., Campbell, P. M., Pincus, M. R., & Bowne, W. B. (2020). Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells. Anticancer research, 40(9), 4857–4867. https://doi.org/10.21873/anticanres.14488

Related reading: PNC-27 and tumor cell lines.

Last updated Oct 30, 2026 · Scientific review: Dr. Dimitar Marinov, MD, PhD