P21

P021, Peptide 021, CNTF-derived peptidergic compound, Ac-DGGL(A)G-NH2 (adamantylated tetrapeptide)

Cognitive & neuro

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Synthetic tetrapeptide mimetic: a four-amino-acid fragment (Asp-Gly-Gly-Leu) derived from the active region of ciliary neurotrophic factor (CNTF), capped and carrying an adamantane group to improve stability and blood-brain-barrier crossing
Mechanism: Reported to raise BDNF expression in the brain and inhibit the LIF/STAT signalling branch of CNTF, boosting new neuron formation and synaptic protein levels without the growth-factor side effects of CNTF itself
Routes studied: Oral (in food or gavage) and intraperitoneal/subcutaneous (mice and rats); oral and subcutaneous (community, uncommon)
Dose range reported: Mice: ~60 mg/kg/day in diet for months (Alzheimer's models); 500 nmol/kg intraperitoneal in earlier studies. Community reports (scarce): 1–5 mg/day subcutaneous or oral. No human dose exists
Half-life: Reported to be stable in plasma for hours in rodents owing to the adamantane cap; human data none
Storage: Lyophilised: refrigerate, protect from light. Reconstituted: refrigerate; community practice is use within ~4 weeks
Regulatory status: Not approved anywhere; no human trials registered as of review date

Doses are as reported in studies or by the community — never recommendations.

1What it is

P21 was developed by Khalid Iqbal's group at the New York State Institute for Basic Research in Developmental Disabilities (Staten Island). CNTF is a natural brain growth factor that supports neuron survival and can trigger new neuron formation, but it is a large protein that does not cross into the brain from blood and caused weight loss and other problems when tried as a drug for ALS in the 1990s. Iqbal's team identified an 11-amino-acid active fragment (Peptide 6), then cut it to four amino acids and added an adamantane cap (a rigid carbon cage also used in the drugs amantadine and memantine) to make a small molecule that survives in blood and reaches the brain. The result is a synthetic research compound, not a naturally occurring peptide.

It has been studied almost entirely by its inventors in mouse models of Alzheimer's disease and ageing. Its appearance in the community is recent and limited.

2How it's thought to work

BDNF induction. P21 increases BDNF expression in the hippocampus, which in turn supports neurogenesis and synaptic plasticity.

CNTF receptor modulation. it is proposed to interfere with the LIF/LIFR component of CNTF signalling, tipping the balance toward neurogenesis and away from the gliogenic effects of full CNTF.

Reduced tau and amyloid pathology. in transgenic mice, chronic P21 reduced abnormal tau phosphorylation (via GSK-3β inhibition) and amyloid-beta levels, alongside behavioural improvement.

Synaptic proteins. raises synaptophysin, PSD-95 and related markers in treated aged or Alzheimer's-model mice.

Proposed: a fragment of ciliary neurotrophic factor reported to promote neurogenesis in the adult hippocampus in animal models. The claim is new neurons rather than a receptor interaction, and it has not been tested in humans.Schematic — not to scale

3What the research shows

Alzheimer's disease mouse models (3xTg-AD, Ts65Dn, Fisher aged rats)

Chronic oral P21 in 3xTg-AD mice, started before or after pathology onset, improved spatial memory, increased neurogenesis and BDNF, reduced tau phosphorylation and amyloid pathology, and rescued synaptic protein loss (Kazim 2014, Neurobiol Dis; Baazaoui & Iqbal 2017, Alzheimers Res Ther). In the Ts65Dn Down syndrome model the parent peptide improved learning and increased neurogenesis (Blanchard 2010). [1][2][4]

Age-related cognitive decline in rats

Aged Fisher rats given P21 showed improved spatial memory with increased hippocampal neurogenesis and dendritic density (Bolognin 2014, Neurobiol Aging). [3]

Traumatic brain injury and other models

Smaller rodent studies report benefit in TBI and in a model of mild cognitive impairment.

Mechanism studies in cultured neurons

In neural progenitor and hippocampal cultures, P21 and its parent Peptide 6 increased neuronal differentiation and dendritic growth, and the effect was associated with raised BDNF and reduced LIF signalling (Li 2010, FEBS Lett; Kazim & Iqbal 2016 review). These are the inventors' own findings. [5][6]

Not gradednone

Human studies

No published human data of any kind. The compound is at the preclinical stage and was last reported as a candidate for Investigational New Drug development, with no trial registered as of review †.

Cognition, "neurogenesis", mood in the community

Anecdotal reports are rare and recent. No basis beyond the rodent data.

4Reported side effects and interactions

Literature-reported

No toxicity reported in chronic rodent studies at effective doses; the authors emphasise the absence of weight loss or the inflammatory effects seen with full CNTF. No formal toxicology is published.

Community-reported

too few reports to characterise; isolated mentions of headache and fatigue.

Theoretical. chronic elevation of neurotrophic signalling has unknown long-term effects; CNTF biology intersects with appetite and metabolism (full CNTF causes weight loss), and whether the fragment retains any such effect in humans is untested. Any growth-factor-pathway carries the usual theoretical concern about pre-existing malignancy. Nothing is known about human pharmacokinetics, brain penetration or safety.

Interactions. none studied.

Markers researchers commonly monitor

Marker	Why it's watched
No compound-specific laboratory markers are established
Body weight and appetite	the only known liability of the parent compound CNTF; worth tracking given the derivation.
Cognitive self-ratings or standardised tests	the sole efficacy readout available.
General baseline panels (CBC, CMP) with the note that no compound-specific markers exist; serum BDNF is sometimes mentioned but is not a validated marker of brain BDNF and is not recommended as such

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied on the research market as powder, typically in 5 mg or 10 mg vials. with , swirl gently, protect from light. Because the molecule carries a hydrophobic adamantane group, solubility can be lower than for typical peptides; community reports describe cloudiness at high concentration.

Open in calculator, pre-loaded →

6Commonly studied alongside

Nothing in the literature. In community discussion it is grouped with Semax, Selank, Dihexa and Cerebrolysin as a "neurotrophic" peptide; no combination data.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Not on the 2023 Category 2 compounding list as far as this review could establish †
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not specifically named; S0 (non-approved substances) applies †

8Open questions

Does P21 cross the human blood-brain barrier and reach meaningful brain concentrations?
Is the mechanism (BDNF induction via CNTF receptor modulation) confirmed independently of the inventing group?
Any human safety data at all — none exist.
Does research-market "P21" match the published compound, given the specific adamantane modification?
Would the rodent doses (tens of mg/kg) translate to anything achievable in humans by the routes the community uses?

9References

1Blanchard J et al. (2010). Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Aβ and tau pathologies in Ts65Dn mice. Acta Neuropathol. PubMed · DOI
2Kazim SF et al. (2014). Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. Neurobiol Dis. PubMed · DOI
3Bolognin S et al. (2014). Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound. Neurobiol Aging. PubMed · DOI
4Baazaoui N, Iqbal K (2017). Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound. Alzheimers Res Ther. PubMed · DOI
5Kazim SF, Iqbal K (2016). Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener. PubMed · DOI
6Li B et al. (2010). Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

25 Oct 2026Profile published — awaiting medical review

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