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Compound monograph

P021 (P21)

P021 is a small acetylated tetrapeptide carrying an adamantane-derived C-terminal extension, designed as a CNTF-derived peptide mimetic.

Published: 2026-09-13Last updated: 2026-10-15Literature/identifier verification: 2026-09-13
Also known asP21P-21Peptide 021
Neurotrophic peptide mimetics

01

Identity & nomenclature

P021 is a small acetylated tetrapeptide carrying an adamantane-derived C-terminal extension, designed as a CNTF-derived peptide mimetic.

P021 is the preferred research designation; P21 is the common commercial spelling. The primary literature identifies it as a peptide mimetic derived from ciliary neurotrophic factor, CNTF. It is not described there as a chemically identified fragment isolated from Cerebrolysin, and that provenance claim should not be repeated.

Canonical name: P021.

Declared aliases and development codes: P21, P-21, Peptide 021.

02

Molecular properties

Molecular formulaC27H42N6O8
Molecular mass578.66 Da
CAS Registry Number1246751-68-7
PubChem CID56599151
UNIIVV8CZC8PAS
Three-letter sequenceAsp–Gly–Gly–Leu–Adamantane-carboxamide
Terminal groupsN-terminal acetylation; C-terminal carboxamide

CRITICAL: the shorthand Ac-DGGLAG-NH2 appears in the primary literature, where AG denotes a single adamantane-derived unit — NOT alanine followed by glycine. Parsed as an ordinary six-residue peptide it yields the wrong molecule, formula and mass. The leucine carbonyl is amide-linked to an amino-substituted adamantane cage bearing a carboxamide. The aspartate side-chain carboxyl is free.

03

Structural characteristics

Reported effects are at the pathway level: LIF-related signalling, and changes in BDNF expression with associated GSK3beta signalling in experimental models. No direct molecular binding target, binding affinity, receptor-subtype selectivity or receptor-level agonist classification is established. P021 should not be described as a direct TrkB agonist or a direct GSK3beta inhibitor on the strength of downstream measurements. The proposed BDNF increase is also not uniformly reproduced: an independent study reports that chronic exposure failed to raise BDNF under its conditions. That result is part of the record for this compound, not an omission.

  • Adamantane-based C-terminal extension

Terminal features: N-terminal acetylation, C-terminal carboxamide.

04

Molecular targets & mechanisms

05

Analytical considerations

For a molecule this size the useful identity package is LC–high-resolution MS with 1D and 2D NMR, supported by fragmentation and amino-acid analysis. NMR matters specifically because 'contains an adamantane group' does not establish the registered connectivity, and a mass-compatible connectivity isomer — including an Asp/isoAsp rearrangement — would not be excluded by an intact-mass match. Asp and Leu configuration need a chiral method. A BDNF-expression assay is not a chemical identity test and is a poor acceptance criterion given the conflicting reports above.

Disagreements and mix-ups

Points where sources disagree about this compound's identity, or where a name or form is easily confused with another, as noted in this record. The discrepancy register quotes the passage for each one.

What the studies reported

Each finding describes one cited study in its stated model. These observations are specific to that study and do not establish effects in other settings.

Cell and tissue studies

  • SH-CDKL5-KO human neuronal model of CDKL5 deficiency disorder

    Mottolese et al. reported that P021 restored deficits in neuronal proliferation, survival and maturation and alterations in GSK3beta signaling in SH-CDKL5-KO cells, a human neuronal model of CDKL5 deficiency disorder.

    Reference [3]

Animal studies

  • Female 3xTg-AD mouse model of Alzheimer disease

    Kazim et al. observed significantly reduced abnormal tau hyperphosphorylation and accumulation at major Alzheimer-associated sites in female 3xTg-AD mice exposed to P021.

    Reference [2]

  • Female 3xTg-AD mouse model of Alzheimer disease

    Kazim et al. reported a significant decrease in soluble amyloid-beta levels with P021 in female 3xTg-AD mice, with only a trend toward reduced plaque load in the hippocampal CA1 region.

    Reference [2]

  • Young and adult male Cdkl5 knockout mouse model of CDKL5 deficiency disorder, C57BL/6N background backcrossed in C57BL/6J

    Mottolese et al. found that P021 failed to increase BDNF levels and did not restore neuroanatomical defects in young and adult male Cdkl5 knockout mice from a C57BL/6N background backcrossed in C57BL/6J for three generations, with very few effects on behavioral performance.

    Reference [3]

06

Verified bibliography

Cited studies by type

The 3 papers this record cites, counted by the kind of work each reports. A count is the size of this record's selection, not of the research that exists, and says nothing about results, safety, effectiveness or approval.

A paper can report more than one kind of work. Each count opens those papers in the bibliography. Compare every record on the Evidence Map.

  1. Reference 1

    Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice.

    Li B, Wanka L, Blanchard J, Liu F, Chohan MO, Iqbal K, Grundke-Iqbal I

    FEBS letters · 2010-06-30 · Journal Article

    current
    PMID 20600002DOI 10.1016/j.febslet.2010.06.025P021 (P21)

  2. Reference 2

    Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease.

    Kazim SF, Blanchard J, Dai CL, Tung YC, LaFerla FM, Iqbal IG, Iqbal K

    Neurobiology of disease · 2014-07-15 · Journal Article

    current
    PMID 25046994DOI 10.1016/j.nbd.2014.07.001P021 (P21)

  3. Reference 3

    Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder.

    Mottolese N, Loi M, Trazzi S, Tassinari M, Uguagliati B, Candini G, Iqbal K, Medici G, Ciani E

    Journal of neurodevelopmental disorders · 2024-11-26 · Journal Article

    current
    PMID 39592934PMC11590213DOI 10.1186/s11689-024-09583-4P021 (P21)

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Li B et al. 2010Study models reported: animal (mouse) · from the abstract
Kazim SF et al. 2014Study models reported: animal (mouse) · from the abstract
Mottolese N et al. 2024Study models reported: in vitro; animal (mouse) · from the abstract

Catalog listing

Record history

Published 2026-09-13.

  • : Sequence and structure

Each entry names the parts of this record that changed on that date. Changes to links between records and to catalogue links are not listed. This history covers the tracked record fields; study findings are not listed here.

Cite this record: Purely Peptides Research Library. P021 (P21). Published 2026-09-13; updated 2026-10-15. https://purelypeptides.org/research/compounds/p021/

10

Methodology & citation verification

Reference identity is checked against official PubMed metadata. Local deterministic receipts bind each normalized title and canonical metadata record to its verification date. Scientific values remain absent when an authoritative source has not been verified.

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