Four-amino-acid fragment of ciliary neurotrophic factor with an adamantane cap, studied for memory in mouse and rat Alzheimer's models.
Also called P021, Peptide 021, Ac-DGGL-adamantyl amide, CNTF peptide mimetic
P21, usually written P021 in the papers, comes from Khalid Iqbal's lab at the New York State Institute for Basic Research. It is four amino acids (Asp-Gly-Gly-Leu) taken from the active region of ciliary neurotrophic factor (CNTF), with an acetyl group on the front and an adamantane amide on the back. The adamantane makes it fat-soluble enough to be mixed into mouse chow and still reach the brain.
In mice and rats it raised brain BDNF, increased the birth of new neurons in the hippocampus, and improved maze and object-recognition scores. In 3xTg Alzheimer's mice it lowered abnormal tau and soluble amyloid-beta. It also helped Down syndrome model mice and aged rats. Nearly all of this work comes from the one lab that invented it, and a 2024 University of Bologna study (with Iqbal as a co-author) found it did not raise BDNF or fix brain structure in living CDKL5 deficiency model mice.
No human has been given P021 in a published study and there is no registered clinical trial. Iqbal holds US patents on CNTF small-molecule peptide mimetics, as disclosed in his 2017 Down syndrome paper. What is sold online as P21 nasal spray or capsules has no human dosing, safety or effect data behind it.
What it binds to, and what happens inside the body after that, step by step.
P021 is designed to mimic the part of CNTF that supports neuron survival, without CNTF's side effects. In rodents it raises BDNF levels, which lowers the activity of the enzyme GSK-3 beta, the main kinase that adds abnormal phosphate groups to tau. The downstream effects reported are more new neurons in the dentate gyrus, more synaptic proteins, and less tau pathology.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
All evidence is from mice, rats and cell lines, and almost all of it comes from the lab that created P021. The rodent results are consistent across Alzheimer's, aging and Down syndrome models, but a 2024 study led by a different group, in a different disease model, saw little benefit in living mice. There is no human data on safety, dose or effect.
No human studies are among the key studies for P21 (P021). Everything known comes from animals or cells.
Female 3xTg-AD and wild-type mice, 12 months of P021 in the diet from age 9-10 months
P021 reduced hyperphosphorylated tau, lowered soluble amyloid-beta, raised BDNF, lowered GSK-3 beta activity and rescued memory and neurogenesis deficits.
Read the studyFemale 3xTg-AD mice treated from 3 months of age for up to 18 months
Starting P021 before plaques formed prevented neurodegeneration and tau and amyloid pathology, rescued episodic memory and markedly reduced mortality.
Read the studyFischer rats aged 22-24 months
Oral P021 reduced age-related learning and memory decline, increased BDNF and neurogenesis, and lowered hippocampal myo-inositol on MR spectroscopy.
Read the studyTs65Dn Down syndrome model mice, treated from before birth to early life
Prenatal to early postnatal P021 prevented developmental delay in pups and hippocampal memory problems in adult mice.
Read the studyNormal adult C57Bl6 mice
Peripheral P21 improved learning and short-term and spatial memory and increased maturation of new neurons in the dentate gyrus.
Read the studyHuman CDKL5-knockout neuron cell line and young and adult Cdkl5 knockout mice (University of Bologna, with Iqbal as co-author)
P021 fixed neuron survival and maturation defects in cells, but chronic treatment in mice did not raise BDNF or correct brain structure and gave limited behavioral benefit.
Read the studyThese are questions the published research has not answered.
No product containing P21 (P021) is approved as a medicine by the FDA.
Preclinical only; no IND or registered human trial found on ClinicalTrials.gov. P021 is not named on the WADA list. As a substance with no government approval for human use it falls under WADA class S0 (non-approved substances); as a growth factor mimetic it could also be read as S2.3. Either way it is banned at all times. Not related to the cell-cycle protein p21 (CDKN1A), which shares the name.
No human half-life has been published for P21 (P021), so we do not draw a clearance curve. Half-lives quoted online for it are usually estimates from animal data.
No human study or approved label has published a dose for P21 (P021), so there is no table to show.
No dose of P21 (P021) has been tested in a published human study or approved on a label. Numbers that circulate online come from animal studies scaled up by guesswork or from sellers. We do not reproduce them.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
Increased neurogenesis was measured in mouse and rat hippocampus tissue. No human study has looked.
It reduced tau and amyloid in transgenic mice. Many compounds have done that and failed in people; P021 has not been tested in a single patient.
The published studies gave P021 in food or by injection to rodents. No paper tests an intranasal product.
Several rodent studies from the originating lab found higher BDNF, but a 2024 Bologna-led study in Cdkl5 knockout mice did not. No human measurements exist.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Online stacks combine two different neurotrophic approaches: a CNTF mimetic and an HGF/c-Met modulator.
EvidenceNo study has tested this combination in any species.
No published stability data exist for the research-grade powder. Research suppliers generally ship it as a freeze-dried powder and list frozen storage (-20 C), dry and away from light; none of this has been independently verified.
No published stability data exist for a reconstituted solution. The usual lab practice for small peptides is refrigeration at 2-8 C and short use windows, but no study has tested how long this compound stays intact once mixed.
One email when a trial reads out, a label changes or the FDA acts on a peptide. Free, no selling of peptides, unsubscribe any time.