Description
What is PNC27?
PNC27 is a 32‑amino‑acid chimeric research peptide developed by the Michael/Pincus/Rosal group. It combines residues 12–26 of the p53 transcriptional‑activation domain (the MDM2/HDM2‑binding sequence) with a C‑terminal membrane‑residency signal derived from the penetratin/Antennapedia homeodomain. In preclinical cancer research it is reported to selectively kill tumor cells displaying HDM2 on their plasma membrane via membrane‑pore formation, sparing normal cells that do not display HDM2 extracellularly.
Mechanism of Action
- Binds surface‑displayed HDM2 on cancer cell membrane
- Forms transmembrane pores, inducing rapid necrotic cell death
- Reported selective cytotoxicity: normal cells lacking surface HDM2 are largely unaffected in preclinical assays
- Independent of p53 status in target cells (mechanism bypasses canonical p53‑MDM2 intracellular signaling)
Compound Properties
- Sequence: PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG (32 aa, N‑terminal p53 domain + C‑terminal penetratin)
- Molecular weight: ~4087 Da
- Form: Lyophilized powder
- Unit size: 10 mg / vial
- Source: Solid‑phase peptide synthesis; ≥95% purity by HPLC
Research‑Reference Dosing
Published research‑reference ranges in preclinical literature:
- Rosal et al., Biochemistry (2004): original PNC27 design and cytotoxicity characterization.
- Michl et al., Clinical & Experimental Metastasis (2010): activity in pancreatic cancer models.
- Sarafraz‑Yazdi et al., PNAS (2010): membrane‑pore mechanism characterization.
- Human clinical trial data is not available; PNC27 remains an investigational research peptide.
Research Findings
- Selective cytotoxicity to HDM2‑surface‑displaying cancer cell lines in vitro (Rosal 2004)
- Efficacy in xenograft pancreatic, breast, and leukemia models (Michl 2010 and others)
- Mechanism of action distinct from canonical MDM2 inhibitors (Nutlin class)
- No published human clinical program as of early 2025
Known Side Effects Reported in Research/Trials
- Generally well tolerated in short‑term rodent studies at research doses
- Injection‑site reactions
- No human safety profile established
- Theoretical concerns with membrane‑active cancer peptides: non‑specific cytotoxicity at higher concentrations, immunogenicity, off‑target effects on normal cells that transiently display HDM2 under stress
Storage & Handling
- Lyophilized (unreconstituted) vials: store at −20°C long‑term; short‑term 2–8°C acceptable.
- After reconstitution with bacteriostatic or sterile water: store at 2–8°C; use within 14–28 days per standard peptide stability guidance.
- Protect from light, heat, and repeated freeze‑thaw cycles. Handle in a sterile laboratory environment.
Certificate of Analysis
A Certificate of Analysis (COA) confirming identity and purity by HPLC / MS is available upon request. Contact Lonestar Peptides for lot‑specific documentation.
Summaries reference peer‑reviewed preclinical and clinical literature available as of early 2025. Newer findings may not be reflected. Researchers should consult current literature and conduct their own due diligence. Lonestar Peptides makes no claim of therapeutic benefit.
