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Lexicon
Cognition

P21

A tiny tetrapeptide derived from CNTF that stimulates neurogenesis in the hippocampus in studies.

2 min read 11 sources

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P21 vial with white powder and the black TPD label on a white podium, next to a blue 3D molecule model in a bright lab
Preclinical · not approved

Summary

At a glance

Sources checked on 26 Oct 2026

Core from CNTF
4 amino acids

from the most active region of CNTF, plus a glycine with an adamantane group5

Longest dosing in the Alzheimer model
12 months

Mice received P021 with their food, tau changes declined1

Age of the rats
22 months

Rats aged 22 to 24 months lost less learning and memory performance3

Human trials in the registry
0 trials

no trial with P021 on ClinicalTrials.gov, as of 26 Oct 202611

  • P21, called P021 in research, is a short peptide from the most active region of the nerve growth factor CNTF. An attached glycine with an adamantane group is meant to make it more stable and able to reach the brain.54
  • It was developed at the New York State Institute for Basic Research. Almost all studies come from this group, all in cells and animals.410
  • In Alzheimer mice a year of dosing with the food reduced abnormal tau changes. Memory, formation of new nerve cells and synaptic plasticity improved.1
  • Old rats lost less learning and memory performance and made more BDNF. The tau level in their cerebrospinal fluid fell to that of young animals.32
  • ClinicalTrials.gov lists no human trial of P021 (as of October 2026). Everything here is preclinical research, not a recommendation.11
Profile

Updated June 2026

Class
CNTF mimetic / BDNF enhancer
Use
Subcutaneous

2x per week

Half-life
short

hence 2 doses per week

Status
Preclinical

small human data

Sizes
10 mg

1 size in the shop

Contents 13 sections
  1. At a glance
  2. What is P21?
  3. How it works
  4. How to take it
  5. Dosing
  6. What the research shows
  7. Research status
  8. Side effects
  9. Storage
  10. Related compounds
  11. FAQ
  12. Glossary
  13. Sources

What is P21?

P21 is a synthetic tetrapeptide - only four amino acids, derived from CNTF (Ciliary Neurotrophic Factor), an endogenous neurotrophin. Small enough to cross the blood-brain barrier and act directly in the brain.

In preclinical studies P21 is among the most potent known neurogenesis enhancers - it stimulates the formation of new neurons in the hippocampus, the brain region for learning and memory.

Comparison

Other peptides focused on the brain

Rough classification by origin. Tap a card to open its entry.

CNTF derivative with adamantane P21 BDNFGSK-3β
ACTH(4-7) derivative Semax Spadin derivative PE 22-28 Tripeptide from the Khavinson programme Pinealon

The origin of the other peptides is described in their lexicon entries. Only for P21 are targets shown here.

How it works

P21 increases BDNF (Brain-Derived Neurotrophic Factor) expression and reduces pathological tau phosphorylation. BDNF acts like fertilizer on synapses - existing connections strengthen, new ones form more easily. The tau effect is interesting in the Alzheimer's context.

Additionally it stimulates adult neurogenesis in the hippocampus - one of the few brain regions where new neurons form at all in the adult brain.

Where it acts

Where P21 acted in experiments

Tap a point or a card. Colour = target, grey = observed. All from cell and animal studies.

  1. Brain (hippocampus)

    More BDNF, less GSK-3β activity and abnormal tau, more new nerve cells (mice, rats)1

    BDNFGSK-3β
  2. Eye (retina)

    Age-related retinal changes slowed in old rats and Alzheimer mice9

    Observed in trials

Known targets1

Compound P021, Ac-DGGL(A)G-NH2 (nicht in PubChem oder ChEMBL): two described targets, type of action on each card.

Neurotrophic factor BDNF
Gene
BDNF
UniProt
P23560
ChEMBL
CHEMBL4523205
Action
Production increased, not a direct binding target
Glycogen synthase kinase 3β
Gene
GSK3B
UniProt
P49841
ChEMBL
CHEMBL262
Action
Activity lowered, probably via more BDNF
Glass nerve cell with a glowing core and branching extensions, blue 3D molecules docking onto several branches and making the spots light up
Symbolic image.

How to take it

P21 is injected subcutaneously into the abdomen (keep clear of the area around the navel), the front and the inner side of the thigh or the back of the upper arm, about 2 times per week. The lyophilized powder in the vial is reconstituted with bacteriostatic water beforehand.

  • Subcutaneous, thin insulin needle.
  • 2x per week is enough thanks to the sustained BDNF effect.
  • Ideally in the morning - P21 is mildly activating.

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

What the research shows

P21 was developed at the New York State Institute for Basic Research and tested in several preclinical studies:

  • Kazim et al. 2014: improved cognition and less tau hyperphosphorylation in an Alzheimer's mouse model.
  • Khatoon et al. 2015: in aged rats tau levels in brain and cerebrospinal fluid dropped. P021 proved blood-brain-barrier permeable.
  • Bolognin et al. 2014: increased BDNF expression and neurogenesis promotion in aged rats, plus a slower decline in learning and memory.

Robust human data is lacking so far - everything is preclinical and small.

Glass seahorse sculpture on a glass base, surrounded by sweeping bands of light in a bright room
The hippocampus is named after its seahorse shape. Symbolic image.

Research status

Where the research stands

So far P021 has been studied in cells, mice and rats, almost only by the group at the New York State Institute for Basic Research and its partners. As of 26 Oct 2026. 11

  1. Preclinical Cell assays, Alzheimer and Down syndrome models in mice, old rats
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 no registered trial
  5. Approval not yet
Not approved and no registered human trial. P021 has only been studied preclinically so far.11

So far there is no registered trial in humans. 11

Side effects

  • Occasional local irritation at the injection site.
  • Some users report mild drive or sleep shifts in the first days.
  • No known serious side effects from preclinical studies.

Storage

Store lyophilized powder dry at normal room temperature (around 20 to 25 degrees), protected from light. After reconstitution, refrigerate - stable for at least 4 to 6 months with barely any loss, in practice considerably longer.

Shelf life

How long it keeps

Undissolved (powder) Dry, cool, protected from light

Store the lyophilised powder dry and dark.

Dissolved (mixed) Fridge

Stable for at least 4 to 6 months with barely any loss.

  • Keep it dark
  • Dissolved: 2 to 8 degrees
  • Note the mixing date on the vial
Nine vials with white powder and blue caps in the door shelf of a bright fridge
Powder dry and dark, once dissolved into the fridge, stable there for at least 4 to 6 months. Symbolic image.

Related

Related compounds

Blends with P21 or a different path: all in the TPD lexicon.

P21
P21-Adamantane Listed as a more stable form, but P021 already carries the adamantane itself Semax Different short peptide focused on the brain Selank Different peptide focused on mood and anxiety PE 22-28 Different peptide, new nerve cells in mice Dihexa Different molecule linked to memory in research Pinealon Short peptide from the Khavinson programme, brain

FAQ

Common questions about P21

Short answers, each backed by the sources below.

Is P21 approved or studied in humans?

No. There is no approval and as of 26 October 2026 ClinicalTrials.gov lists no trial with P021. According to a conflict of interest statement from 2024 a company of the developer intends to develop P021 as a medicine. So far all data come from cells and animals.1110

What is P21 made of?

Of a tetrapeptide from the most active region of CNTF, plus a glycine with an adamantane group at the end. The formula is Ac-DGGL(A)G-NH2. The adamantane is meant to ease the way into the brain and slow breakdown by enzymes. The first paper from 2010 called the peptide P21, later ones P021.541

What did the Alzheimer models show?

Mice with three Alzheimer genes received P021 for twelve months from an age of 9 to 10 months. Abnormal tau declined clearly, soluble amyloid fell, memory and the formation of new nerve cells improved. When dosing started at 3 months, tau and amyloid changes largely did not appear and fewer animals died. Even dosing only before and shortly after birth later reduced tau changes and amyloid plaques.1658

What did old rats show?

Rats aged 22 to 24 months lost less learning and memory performance with P021 and made more BDNF and more new nerve cells. A second paper showed that P021 reaches the brain and lowered the tau level in the cerebrospinal fluid to that of young rats, but not amyloid.32

Are there findings outside Alzheimer's?

Yes, mixed ones. In a mouse model of Down syndrome dosing before and shortly after birth prevented developmental delay and later memory problems. In a model of CDKL5 disorder P021 helped in cell culture, but in mice BDNF did not rise and the benefit stayed small.710

How was P021 given in the studies?

In the animal studies mostly with the food, so by mouth, often over many months. The lexicon entry instead describes dosing under the skin. There are no human data on that.15

Which side effects are known?

There are no solid data because P021 has never been tested in humans. In old rats it caused no detectable immune reaction. That cannot be transferred to humans.211

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Adamantane
A small cage-like hydrocarbon scaffold. On peptides it is meant to slow breakdown and ease the way into the brain.
BDNF
Brain-derived neurotrophic factor: a growth factor in the brain, important for synapses, learning and new nerve cells.
Blood-brain barrier
A tight wall of the brain's blood vessels that keeps many substances in the blood out.
CNTF
Ciliary neurotrophic factor: the body's own growth factor that keeps nerve cells alive. P21 is derived from its most active region.
Hippocampus
Brain region for learning and memory.
Lyophilisate
Freeze-dried powder. Without water a peptide keeps much longer.
Neurogenesis
Formation of new nerve cells. In adults it mainly takes place in the hippocampus.
Preclinical
Research before first use in humans, in cell cultures and animal models. Results cannot be transferred directly to humans.
Subcutaneous
Into the fat layer just under the skin.
Tau
A protein that supports the scaffold of nerve cells. In Alzheimer's it is excessively phosphorylated and clumps together.

Evidence

Sources

Show all 11 sourcesHide sources 10 Studies1 Trial registry checked 26 Oct 2026

Studies

  1. P021 over one year in an Alzheimer mouse model

    Kazim et al., Neurobiology of Disease, 2014

    DOI 10.1016/j.nbd.2014.07.001 PMID 25046994
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. P021 reaches the brain and lowers tau in the cerebrospinal fluid of old rats

    Khatoon et al., Journal of Alzheimer's Disease, 2015

    DOI 10.3233/JAD-142799 PMID 26401692
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. P021 slows memory loss in old rats

    Bolognin et al., Neurobiology of Aging, 2014

    DOI 10.1016/j.neurobiolaging.2014.02.017 PMID 24702821
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. First paper on P21: peptides with adamantane and memory in mice

    Li et al., FEBS Letters, 2010

    DOI 10.1016/j.febslet.2010.06.025 PMID 20600002
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Early P021 dosing protects synapses in an Alzheimer model

    Baazaoui und Iqbal, Alzheimer's Research and Therapy, 2017

    DOI 10.1186/s13195-017-0273-7 PMID 28655344
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  6. Early P021 dosing prevents amyloid and tau changes (mice)

    Baazaoui und Iqbal, Journal of Alzheimer's Disease, 2017

    DOI 10.3233/JAD-170075 PMID 28387677
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  7. P021 before and after birth in a Down syndrome model (mice)

    Kazim et al., Scientific Reports, 2017

    DOI 10.1038/srep45561 PMID 28368015
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  8. P021 before and shortly after birth in an Alzheimer model (mice)

    Wei et al., Alzheimer's Research and Therapy, 2020

    DOI 10.1186/s13195-020-00666-7 PMID 32854771
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  9. P021 and age-related retinal changes (rats, mice)

    Liu et al., Frontiers in Aging Neuroscience, 2019

    DOI 10.3389/fnagi.2019.00309 PMID 31803044
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  10. P021 in a model of CDKL5 disorder (cells and mice)

    Mottolese et al., Journal of Neurodevelopmental Disorders, 2024

    DOI 10.1186/s11689-024-09583-4 PMID 39592934
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)

Trial registry

  1. Search on ClinicalTrials.gov (no trial with the peptide)

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

In the shop

P21 in the catalog

Sizes, prices and shipping times are on the product page.

To the product