Product Overview

PNC-27

PNC-27 is a synthetic 32–residue peptide that fuses the p53 HDM-2–binding domain (aa 12–26) to a cell-penetrating leader sequence, enabling selective targeting and killing of cancer cells that present HDM-2 on their plasma membranes—sparing normal, untransformed cells.[1–4]

Mechanism of Action

  • Binds the p53-binding site of HDM-2 (aa 1–109) on cancer cell membranes, forming a 1:1 complex that triggers transmembrane pore formation → rapid necrosis via membrane disruption and loss of integrity.[1,5–7]
  • Immuno-EM and colocalization studies show PNC-27 and HDM-2 assemble as ring-like structures lining the pores.[1,5]

Spectrum of Activity

  • Cytotoxic to diverse solid and hematologic malignancies (breast, pancreatic, colon, cervical, ovarian; AML; p53-null leukemia) and to cancer stem-like cells expressing membrane HDM-2; induces tumor-nodule necrosis in vivo.[2–4,8,9]

Selectivity & Safety

  • Normal cells (e.g., fibroblasts, lymphocytes, untransformed epithelia) lack membrane HDM-2 and resist lysis; forced membrane-localization of HDM-2 confers susceptibility—confirming target specificity.[1–3,7]

Additional Mechanisms

  • Also disrupts mitochondrial membranes in cancer cells, augmenting cell death; activity requires the intact peptide (both N- and C-termini).[6,7]

Synergy with Chemotherapy

  • Shows synergy with paclitaxel in ovarian cancer models, targeting chemotherapy-surviving cells with increased membrane HDM-2.[9]

Summary

By selectively engaging membrane-bound HDM-2 to form cytolytic pores—while sparing normal cells—PNC-27 presents a distinctive, target-directed approach for oncology research, with supportive data across multiple tumor types and combinational strategies.[1–9]

References

  1. Sarafraz-Yazdi E, Bowne WB, Adler V, et al. PNAS. 2010;107(5):1918-23.
  2. Krzesaj PK, Seydafkan S, Miller AI, et al. Ann Clin Lab Sci. 2025;55(3):347-353.
  3. Davitt K, Babcock BD, Fenelus M, et al. Cancer Chemother Pharmacol. 2010;66(2):325-331.
  4. Thadi A, Morano WF, Khalili M, et al. Anticancer Res. 2021;41(1):27-42.
  5. Sarafraz-Yazdi E, Mumin S, Cheung D, et al. Biomedicines. 2022;10(5):945.
  6. Krzesaj P, Adler V, Feinman RD, et al. Ann Clin Lab Sci. 2024;54(2):137-148.
  7. Sookraj KA, Bowne WB, Adler V, et al. Cancer Chemother Pharmacol. 2010;66(2):325-331.
  8. Thadi A, Lewis L, Goldstein E, et al. Anticancer Res. 2020;40(9):4857-4867.
  9. Alagkiozidis I, Gorelick C, Shah T, et al. Ann Clin Lab Sci. 2017;47(3):271-281.

All information provided is for research purposes only.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY. The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.