Peptides›Cognitive, Other›PNC-27

PNC-27

/ Synthetic 32-residue peptide combining an HDM-2 (MDM2) binding region from p53 with a membrane-residency leader; designed for tumour-selective membrane disruption

TIER 3 · PreclinicalN = 0 · TESTING PENDING

ALIAS · HDM-2 binding peptide · PNC-27 · PNC peptide-27

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · —CLASS · Synthetic 32-residue peptide combining an HDM-2 (MDM2) binding region from p53 with a membrane-residency leader; designed for tumour-selective membrane disruptionCATEGORY · Cognitive, Other

Tier 3. Preclinical anticancer literature in cell lines and rodent xenograft models, predominantly from the Bowne / Pincus group in Brooklyn. Some early-phase clinical activity reported in conference abstracts; no Phase 2 or later trials in the peer-reviewed literature. Pepticker categorises this molecule under 'cognitive' for indexing reasons; the published evidence base is in oncology and the cognitive grouping is a vendor-list artefact rather than a reflection of the science.

§ B · Mechanism of action

PNC-27 fuses a region of the p53 N-terminal transactivation domain that binds HDM-2 (the human MDM2 ortholog and a principal negative regulator of p53) with a membrane-residency signal sequence. The proposed mechanism is selective accumulation at the plasma membrane of cancer cells expressing surface or near-surface HDM-2, with subsequent membrane pore formation and necrotic death. Tumour selectivity is attributed to differential HDM-2 surface expression on transformed versus normal cells.

§ C · Human clinical evidence

Tier 3. Multiple cell-line studies (melanoma, leukaemia, breast, pancreatic, glioblastoma) and rodent xenograft experiments from the originating group report tumour-selective cytotoxicity. Independent replication outside the Bowne / Pincus collaboration is limited. Some Phase 0 / first-in-human activity has been reported in conference and abstract form; the Phase 2 or later peer-reviewed clinical literature does not exist.

§ D · Primary literature

PubMed20182728Sookraj KA et al. — The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide · Cancer Chemotherapy and Pharmacology · in-vitroPNC-27 induced tumour cell lysis as the intact peptide across cancer cell lines, with mechanism characterised as membrane-localised necrosis dependent on plasma-membrane HDM-2.Limitations: In-vitro model systems; from the originating Bowne / Pincus research collaboration.2010

PubMed25117093Davitt K et al. — The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells · Annals of Clinical and Laboratory Science · in-vitroPNC-27 induced necrotic cell death in a poorly differentiated human leukaemia cell line, dependent on HDM-2 expression in the plasma membrane, supporting the membrane-localised tumour-selective mechanism proposed by the originating group.Limitations: Single cell line; in vitro; from the originating research collaboration.2014

§ F · Safety signal

No Phase 1 or later human safety database in the peer-reviewed literature. Preclinical reports describe selective tumour cytotoxicity with apparent sparing of normal cell lines in vitro; in-vivo human safety has not been characterised.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The principal gaps are limited independent replication, absence of peer-reviewed Phase 1 or 2 data, and a research programme concentrated in one collaborating group. Vendor-sold PNC-27 is positioned as a research peptide for cancer cell-line work; cell-line cytotoxicity is not the same as clinical efficacy, and the translational distance is large. The 'cognitive' category in vendor listings does not correspond to any published cognitive indication.