PNC-27 (p53-HDM2 Membrane-Targeting Chimeric Peptide)
✅ ~32-aa chimeric peptide — p53(12-26) HDM2-binding helix + membrane-residency peptide
✅ Binds anomalous cancer-cell surface HDM2 → membrane lysis (not classical apoptosis)
✅ Tumour-cell-selective necrotic killing; spares normal cells (no surface HDM2)
✅ Active in p53-mutant tumours where nutlin-type inhibitors fail
✅ Bowne/Pinto/Michl Albert Einstein chimeric peptide design; MW ~3,800 Da
PNC-27 contains synthetic p53-HDM2 chimeric research peptide.
✓ Verificat medical de Morgan Ellis — Cercetător farmaceutic · 8 ani de experiență · Ultima recenzie: mai 2026
Quick Answer — What is PNC-27?
PNC-27 is a synthetic chimeric peptide (~32 amino acids) developed at Albert Einstein College of Medicine (Bowne, Pinto, Michl, Rauschmayer, Brower et al.) that fuses two functional domains: an HDM2-binding helix derived from p53 transactivation-domain residues 12–26 (sequence PPLSQETFSDLWKLL) and a membrane-residency peptide (MRP) appended to anchor and disrupt cancer-cell plasma membranes. The mechanistic premise is that HDM2 (the human homologue of MDM2) is anomalously expressed on the plasma membrane surface of cancer cells — not just in the nucleus where it normally degrades p53. PNC-27 binds the surface-exposed HDM2, the MRP domain then disrupts the lipid bilayer, and cancer cells undergo rapid membrane lysis and necrotic cell death. Published in pancreatic, leukaemia, breast cancer, and other tumour models. For laboratory research use only. Tumour-targeted membrane-disrupting chimeric peptide.
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| Specificații | Detaliu |
|---|---|
| Compound Class | Synthetic ~32-aa chimeric peptide; tumour-targeted membrane-disrupting therapeutic peptide; HDM2-binding helix + membrane-residency peptide (MRP) chimera |
| Chemical Name | PNC-27 (Peptide Nuclear Construct 27; synonyms: p53-MRP chimera, p53(12-26)-MRP construct) |
| Număr CAS | Research-grade chimeric peptide — no single canonical CAS; identification by published sequence and supplier COA |
| Secvență | N-terminal HDM2-binding helix (p53 transactivation residues 12–26): PPLSQETFSDLWKLL; linker; C-terminal membrane-residency peptide (MRP, sequence varies slightly across published references — researchers should consult COA for exact batch sequence). Total ~32 amino acids. |
| Greutate moleculară | ~3,800 Da (depending on exact MRP sequence) |
| Formula moleculară | ~32-residue chimeric peptide — sequence-derived approximate MF C173H278N52O43S; published MW ~3,800 Da (depending on exact membrane-residency-peptide linker; consult batch COA). |
| Mecanism de acțiune | Tumour-cell-selective membrane lysis. (1) PNC-27 binds HDM2 on the plasma membrane of cancer cells. Normal cells express HDM2 only in the nucleus (where it ubiquitinates and degrades p53 to control p53 levels); cancer cells anomalously express HDM2 on the cell surface — a tumour-specific marker. (2) Once bound, the membrane-residency peptide (MRP) domain inserts into the lipid bilayer. (3) Multimerisation of bound PNC-27 molecules creates membrane pores → rapid necrotic cell death within minutes to hours. The mechanism is necrotic-membrane-lysis (NOT classical apoptosis) — distinguishing PNC-27 from caspase-pathway anticancer peptides. |
| Tumour-Cell Selectivity | Published research has demonstrated selective cancer-cell killing in pancreatic adenocarcinoma, AML and ALL leukaemia, breast cancer, prostate cancer, melanoma, and other tumour models — with sparing of matched normal-cell controls that lack surface HDM2 expression. |
| Formă | Lyophilized white-to-off-white powder; single-use research vials |
| Puritate | ≥99% (HPLC verified, COA on request); MALDI-TOF mass-confirmed at the chimera-specific MW |
| Depozitare | Lyophilized: 2–8 °C short-term, −20 °C long-term. Reconstituted: 2–8 °C, use within 30 days. Avoid repeated freeze-thaw. |
| Utilizare în cercetare | For laboratory research use only. Not for human or veterinary diagnostic or therapeutic use. PNC-27 is a preclinical research tool that has not entered formal clinical development. Not on the WADA Prohibited List. |
Mechanism of Action — HDM2-Targeted Membrane Lysis
PNC-27 was developed by the Bowne / Pinto / Michl / Rauschmayer group at Albert Einstein College of Medicine as an example of chimeric peptide drug design applied to oncology — pairing a tumour-targeting domain (the p53-derived HDM2-binding helix) with a generic killer domain (the membrane-residency peptide). The design logic:
- HDM2 as tumour-specific surface marker — Bowne, Michl et al. discovered that HDM2 (the human MDM2 homologue, normally a nuclear E3 ligase that ubiquitinates p53 for degradation) is anomalously expressed on the plasma membrane surface of essentially all cancer cell lines they tested, but not on matched normal cells. This makes membrane HDM2 a near-universal cancer-cell surface marker.
- p53(12-26) helix as HDM2-binding ligand — Residues 12–26 of the p53 transactivation domain (PPLSQETFSDLWKLL) form an α-helix that is the natural HDM2-binding interface; HDM2 normally captures this helix to ubiquitinate p53. PNC-27 borrows this helix as the homing domain. The peptide binds HDM2 at the same site nutlin small-molecule HDM2 inhibitors target, but with the natural p53-helix geometry.
- Membrane-residency peptide (MRP) as killer domain — Once anchored to surface HDM2, the C-terminal MRP domain inserts into the lipid bilayer. The amphipathic geometry of the MRP, plus oligomerisation of bound PNC-27 molecules on the cancer-cell surface, produces transmembrane pores within minutes.
- Necrotic cell death — Pore formation causes rapid loss of membrane integrity, osmotic lysis, and necrotic cell death — distinct from the slow apoptotic cascade triggered by classical small-molecule HDM2 inhibitors (which work by stabilising p53 to allow downstream p53-mediated apoptosis). PNC-27’s necrotic mechanism is rapid (minutes to hours) and does not depend on functional p53 in the tumour cell — making it potentially useful in p53-mutant tumours where nutlin-type inhibitors are inactive.
- Normal-cell sparing — Normal cells lack surface HDM2 (HDM2 is normally only nuclear), so PNC-27 has no anchoring site on normal cells and does not produce significant membrane-lysis. Published research has demonstrated this selectivity in matched cancer-vs-normal cell pair comparisons across multiple tumour types.
Aplicații de Cercetare Publicate
- Chimeric peptide oncology drug design — canonical example of homing-domain + killer-domain chimera applied to cancer (alongside Adipotide / FTPP in the same paradigm)
- Pancreatic cancer research — most-published tumour type for PNC-27 efficacy work (pancreatic adenocarcinoma is HDM2-high and conventionally hard to treat)
- Leukaemia research — AML and ALL cell-line research; combination with conventional chemotherapeutics
- p53-mutant cancer research — unlike nutlin-type small-molecule HDM2 inhibitors (which require functional p53), PNC-27 is mechanistically active in p53-mutant tumours — useful tool for that subset
- Surface HDM2 biology research — PNC-27 binding is one of the canonical assays for surface-HDM2 detection in cancer-cell biology
- Necrotic vs apoptotic cell-death pharmacology — useful reference compound for membrane-lysis vs caspase-cascade dissection in cell-death research
For broader context on tumour-targeted membrane-disrupting chimeric peptides, see Adipotide / FTPP (vascular-targeted apoptosis fat-loss chimera — same homing+killer paradigm applied to adipose tissue). See also BPC-157 (recovery peptide), TB-500 (recovery peptide), and the full peptides catalog.
Available Strengths
| Putere flacon | Dimensiuni pachet |
|---|---|
| 5 mg — entry research protocols, dose-titration in tumour-cell culture | 10 sau 20 flacoane |
| 10 mg — extended protocols, large-cohort murine xenograft research; lowest per-mg cost | 10 sau 20 flacoane |
Depozitare și reconstituire
Store lyophilized vials at 2–8 °C; freeze unopened at −20 °C for long-term. Reconstitute with bacteriostatic water (1.0 mL per 5 mg vial → 5 mg/mL; 1.0 mL per 10 mg vial → 10 mg/mL). Swirl gently. Store reconstituted at 2–8 °C, use within 30 days. Avoid repeated freeze-thaw. The amphipathic MRP domain may show transient foaming on initial reconstitution — let settle before use.
FAQ
How is PNC-27 different from small-molecule HDM2 inhibitors like nutlin?
Small-molecule HDM2 inhibitors (nutlin-3, idasanutlin, MI-77301) compete with p53 for the same nuclear-HDM2 binding pocket — stabilising p53 to allow downstream apoptosis. They require functional p53 in the tumour to work. PNC-27 acts entirely differently: it binds surface HDM2 (anomalously expressed on cancer cells) and triggers necrotic membrane lysis without requiring functional p53. PNC-27 is therefore active in p53-mutant tumours where nutlin-type inhibitors are not.
What published dose ranges have been used in research?
In-vitro tumour-cell cytotoxicity assays typically use 1–50 µM PNC-27 in culture medium. Murine xenograft research has used 5–20 mg/kg IP, daily or every-other-day, for 2–4 weeks. Researchers should consult Bowne, Pinto, Michl, Rauschmayer published work for protocol-specific guidance.
Is PNC-27 in clinical trials?
PNC-27 remains a preclinical research compound; no formal Phase I/II/III human clinical trials have been completed to date. It continues to be cited as the canonical example of HDM2-surface-targeted chimeric peptide drug design.
Can PNC-27 be combined with chemotherapy in research?
Yes — published research has examined PNC-27 in combination with gemcitabine (pancreatic cancer), cytarabine (AML), and other conventional chemotherapeutics, with broadly additive or super-additive cytotoxicity reported.
Other Chimeric / Targeted Research Peptides
- Adipotide / FTPP — Vascular-targeted apoptosis chimera (adipose-tissue homing + D(KLAKLAK)₂ killer) — same homing+killer paradigm
- BPC-157 — Recovery and tissue-repair pentadecapeptide
- TB-500 — Thymosin Beta-4 fragment, soft tissue recovery
- GHK-Cu — Copper-binding tripeptide, skin and connective tissue research
- Full peptide catalogue
- Apă BAC (Apă bacteriostatică) — Required for reconstituting any lyophilized vial — sterile, 0.9% benzyl-alcohol-preserved diluent
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| Concentrație | 5 mg, 10 mg |
|---|---|
| Cantitate | 10 Viale, 20 Viale, 30 Viale |
PNC-27 (p53-HDM2 Membrane-Targeting Chimeric Peptide)
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PNC-27 (p53-HDM2 Membrane-Targeting Chimeric Peptide)
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