PNC-27
Preclinical ResearchPNC-27
An experimental anticancer peptide designed to bind HDM-2 and form membrane pores in cancer cells. Evidence is entirely preclinical.
Dose
Research protocols vary, no standard human dose established
Route
Subcutaneous injection, Intravenous (research)
Cycle
Research protocols vary, often weeks to months in animal studies
Storage
2°C to 8°C (refrigerator) for extended periods; short-term storage at room temperature is acceptable prior to reconstitution
What is PNC-27?
PNC-27 is a synthetic peptide based on the HDM-2 binding domain of the p53 tumor suppressor protein. It is designed to bind to HDM-2 (human double minute 2 homolog) on the cell surface of cancer cells and subsequently induce selective pore formation in the plasma membrane of these cells, leading to cancer cell necrosis. Research suggests PNC-27 targets tumor cells while sparing normal cells, primarily through an interaction with HDM-2 which is overexpressed and often localized on the plasma membrane of many cancer cells. All current evidence is derived from preclinical (in vitro and animal) studies.
Key Benefits
- Selective cancer-cell membrane disruption (in vitro)
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Molecular Information
Molecular weight
4261.7 g/mol
Length
32 amino acids
Type
Synthetic Peptide
Amino acid sequence
H-Arg-Ala-Ala-Val-Ala-Lys-Lys-Lys-Lys-Ala-Ala-Leu-Ala-Leu-Ala-Leu-Ala-Lys-Lys-Lys-Lys-Ala-Ala-Val-Leu-Leu-Val-Lys-Lys-Lys-Lys-COOH
PNC-27 is a synthetic peptide derived from the p53 tumor suppressor protein's HDM-2-binding domain (residues 12-26), with modified N- and C-termini.
Pharmacokinetics
Time to peak
Null
Half-life
Not established in published data; a short peptide expected to clear rapidly from plasma
Time to clear
Null
No human pharmacokinetic data available.
Research Indications
Selective Cancer Cell Cytotoxicity
In vitro studies demonstrate PNC-27's ability to selectively induce necrosis in various cancer cell lines (e.g., pancreatic, breast, lung, ovarian, colon) while sparing normal cells. Evidence is exclusively preclinical.
Tumor Growth Inhibition
In vivo animal studies using xenograft models (e.g., nude mice implanted with human cancer cells) have shown that PNC-27 administration can significantly inhibit tumor growth and reduce tumor volume. Evidence is exclusively preclinical.
Membrane Pore Formation
Research suggests PNC-27 targets HDM-2 on the surface of cancer cells, leading to membrane pore formation and subsequent cell lysis. This mechanism has been observed in various cancer cell lines. Evidence is exclusively preclinical.
Research Protocols
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Evaluate In Vitro Cancer Cell Cytotoxicity | 0.1 to 100 µM | Single application (continuous exposure for 24-72 hours) | Cell culture medium |
| Assess In Vivo Tumor Growth Inhibition (Mouse Xenograft Model) | 2-10 mg/kg | Daily or 3-5 times per week | Subcutaneous (SC) or Intravenous (IV) |
| Investigate Membrane Disruption Mechanism (In Vitro) | 1 to 10 µM | Single application (short-term exposure, e.g., minutes to hours) | Cell culture medium |
| Evaluate Systemic Toxicity in Animal Models | Up to 20 mg/kg | Daily | Subcutaneous (SC) or Intravenous (IV) |
Dosing frequency and duration are highly dependent on the specific research question and animal model being used. Researchers typically refer to published literature for guidance.
Peptide Interactions
- Monitor Combination
Cisplatin (or other chemotherapeutics)
Some preclinical studies explore combination therapies. While PNC-27's mechanism is distinct, potential synergistic or antagonistic effects with conventional chemotherapies require careful investigation in preclinical models.
- Monitor Combination
HDM-2 inhibitors (small molecules)
Given PNC-27's interaction with HDM-2, co-administration with small molecule HDM-2 inhibitors could theoretically alter its binding or efficacy. Research is needed to understand potential effects in preclinical settings.
- Use Caution
Anticoagulants
As with any injectable compound, potential interactions with blood thinners are a general concern, though specific data for PNC-27 are lacking. Monitor animal subjects for unusual bleeding or bruising at injection sites.
How to Reconstitute
- 1Gather necessary supplies: PNC-27 lyophilized powder vial, bacteriostatic water for injection, sterile syringe, and alcohol wipes.
- 2Remove the protective cap from the PNC-27 vial and wipe the rubber stopper with an alcohol wipe.
- 3Draw the desired amount of bacteriostatic water into the sterile syringe. A common reconstitution ratio is 1ml per 5mg of peptide, but this can be adjusted based on desired concentration.
- 4Slowly inject the bacteriostatic water into the PNC-27 vial, aiming the stream at the side of the vial rather than directly onto the powder.
- 5Gently swirl or slowly invert the vial until the powder is completely dissolved. Do not shake vigorously.
- 6Once dissolved, the solution should be clear. If particles remain or the solution is cloudy, do not use.
Care should be taken to gently swirl or invert the vial rather than shaking to prevent denaturation of the peptide.
What to Expect
- In vitro: Selective binding to HDM-2 on cancer cell membranes.
- In vitro: Formation of pores in cancer cell membranes, leading to cell death.
- Animal studies: Reduction in tumor growth or tumor volume in various cancer models.
- Animal studies: Potential for reduced toxicity to normal cells compared to traditional chemotherapies.
- Animal studies: Observed anti-tumor effects often depend on the specific cancer type and model.
- Preclinical: Potential for membrane-lytic activity, leading to cell disruption.
Side Effects & Safety
- PNC-27 is for research purposes only and not for human consumption or therapeutic use.
- All current data on PNC-27 is from in vitro and animal studies; human safety data is non-existent.
- Handle with appropriate personal protective equipment (gloves, eye protection) in a laboratory setting.
- Dispose of unused peptide and waste materials according to institutional biosafety guidelines.
- Potential for immune response or localized irritation at injection sites in animal models, though not extensively studied for PNC-27 specifically.
- The exact mechanism of selectivity and potential off-target effects in complex biological systems are still under investigation.
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