PNC-27

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PNC-27 — p53(12–26)–Penetratin Chimeric Peptide (HDM-2–Targeting, Pore-Forming Senolytic-Like Agent)

PNC-27 is a chimeric peptide that joins the p53 residues 12–26 (the HDM-2/MDM2-binding domain) to a cell-penetrating leader sequence (penetratin/MRP). In research models it binds HDM-2 present on cancer-cell membranes, assembling into complexes that form transmembrane pores and cause selective necrotic death of malignant cells while sparing untransformed cells. [oai_citation:0‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)

Identifiers

Synonyms: p53(12–26)-penetratin peptide; PNC27
Sequence components: p53_12–26 = PPLSQETFSDLWKLL; leader = RQIKIWFQNRRMKWKK (penetratin). Total length ≈ 32 aa. [oai_citation:1‡PubMed](https://pubmed.ncbi.nlm.nih.gov/11606716/?utm_source=chatgpt.com)
CAS No.: 1159861-00-3 [oai_citation:2‡MedChem Express](https://www.medchemexpress.com/pnc-27.html?srsltid=AfmBOoow354I-LNIB1x1vIYzsMl4BjnGTcFXEwAlO5KJcUnTfvI8BxGK&utm_source=chatgpt.com)
Typical MW / formula (supplier ref.): ~4031.7 Da; C₁₈₈H₂₉₃N₅₃O₄₄S. [oai_citation:3‡abmole.com](https://www.abmole.com/products/pnc-27.html?srsltid=AfmBOoqHflcvJa4BLQ4LA264pM9apSmS4l1ptC0_20CDDAkeaa-enK5S&utm_source=chatgpt.com)
Target: HDM-2 (membrane-associated in malignant cells) [oai_citation:4‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)

How It Works (Plain English)

Finds HDM-2 on cancer-cell membranes and binds via the p53(12–26) motif. [oai_citation:5‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)
Self-associates into pores with HDM-2 complexes → rapid membrane permeabilization and necrosis of malignant cells (“poptosis”). [oai_citation:6‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)
Spares normal cells in many models because untransformed cells lack membrane HDM-2. [oai_citation:7‡annclinlabsci.org](https://www.annclinlabsci.org/content/44/3/241.full?utm_source=chatgpt.com)

Why Researchers Use It

To study senescence/tumor burden reduction via selective killing of malignant or senescent-like cells. [oai_citation:8‡VIVO](https://vivo.weill.cornell.edu/display/pubid38802154?utm_source=chatgpt.com)
To probe HDM-2 biology at the plasma membrane and protein–protein interaction-derived pore formation. [oai_citation:9‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC9138867/?utm_source=chatgpt.com)
To contrast peptide senolytics with small-molecule approaches in fibrosis or solid-tumor models. [oai_citation:10‡IIAR Journals](https://ar.iiarjournals.org/content/40/9/4857?utm_source=chatgpt.com)

Key Study Themes — What Was Tested, What Changed, Why It Matters

Selective Killing of Cancer Cells

What was tested: Solid-tumor and hematopoietic cell lines ± PNC-27; parallel assays in normal/untransformed cells.
What changed: Preferential necrosis of malignant cells with little effect on normal cells, correlating with membrane HDM-2 presence.
Why it matters: Supports HDM-2–dependent selectivity and motivates pore-forming mechanism studies. [oai_citation:11‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)

Pore Formation & “Poptosis” Mechanism

What was tested: Imaging/biophysical assays (electron microscopy, dye-leakage, mitochondrial/lysosomal tracers).
What changed: Membrane pores lined by PNC-27/HDM-2 complexes; mitochondrial disruption observed in treated cancer cells.
Why it matters: Differentiates necrotic pore-driven death from classic p53-apoptosis. [oai_citation:12‡PubMed](https://pubmed.ncbi.nlm.nih.gov/35625682/?utm_source=chatgpt.com)

Fibrosis & Tissue Models (Exploratory)

What was tested: HDM-2/ECM signaling and myofibroblast endpoints in preclinical models.
What changed: Reduced myofibroblast markers and ECM deposition when senescent/aberrant cells were targeted.
Why it matters: Suggests use as a tool compound in fibrosis biology alongside other senotherapeutics. [oai_citation:13‡IIAR Journals](https://ar.iiarjournals.org/content/40/9/4857?utm_source=chatgpt.com)

Potential Research Applications

Cancer Cell Biology

HDM-2 membrane expression, pore-forming cytotoxicity, tumor selectivity assays.

Senescence / SASP Studies

Clearance of senescent-like cells; cytokine/SASP profiling post-ablation.

Fibrosis & Remodeling

ECM turnover, myofibroblast differentiation, organ-specific remodeling models.

Synergistic / Comparator Agents

FOXO4-DRI

Why compare: Peptide senolytic via p53/FOXO4 dissociation (apoptosis) vs PNC-27 pore-driven necrosis.

Navitoclax (BCL-2 family inhibitor)

Why compare: Small-molecule senolytic mechanism vs peptide HDM-2/membrane-pore approach.

Controls

Penetratin alone or p53(12–26) alone to confirm requirement for the chimera. [oai_citation:14‡CDC Stacks](https://stacks.cdc.gov/view/cdc/200685?utm_source=chatgpt.com)

What’s in the Vial (Editable)

Active	Per Vial	Grade / Purity
PNC-27 (p53_12–26–penetratin chimera)	10 mg (set per SKU)	Research-grade, ≥ 98–99% (HPLC/MS)
Appearance	White to off-white lyophilized powder
Storage	Store ≤ −20 °C, desiccated; protect from light

Specifications & Handling

Reconstitution (lab use): Sterile aqueous buffer; record solvent, concentration, pH, and time-to-assay; avoid repeat freeze–thaw.
Stability: Follow peptide-handling best practices; confirm identity/purity by HPLC/MS with each lot.

Assay design: Include normal-cell controls (HDM-2 negative), dye-leakage/pore assays, and HDM-2 blocking where applicable. [oai_citation:15‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)

Known Concerns (Context)

Translational status: Evidence is largely preclinical; limited human data. [oai_citation:16‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)
Selectivity depends on target: Membrane HDM-2 expression varies by model; verify target presence to avoid off-target effects. [oai_citation:17‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2836618/?utm_source=chatgpt.com)
General: For laboratory research use only; not for human consumption, medical, or veterinary use.

Regulatory & Use Notice

Sold for laboratory research use only. Not for human consumption, medical, or veterinary use. No human-use instructions are provided. Buyer is responsible for safe handling and regulatory compliance.

PNC-27 Research Peptide | p53(12–26)–Penetratin Chimera | HDM-2 Targeting, Pore Formation & Selective Tumor Cytotoxicity

Keywords: PNC-27, p53 peptide, penetratin, HDM-2, pore formation, poptosis, senolytic peptide, cancer selectivity, Base Peptides.

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Instructions are NOT provided before or after purchase.

Peptide molecules are unfinished and require reconstitution from a skilled and licensed professional to activate the compound into liquid form. Instructions are not provided for reconstitution, dosing, or adminstration. All products are strictly intended for research purposes and laboratory experimentation. Handling should be by skilled licensed and credentialed professionals only. Non experimental use is strictly prohibited.

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