P21 Research & Listing Availability
Current P21 vial offers are unavailable in this comparison. Research information remains available; this does not establish permanent discontinuation.
Current P21 vial offers are unavailable in this comparison. Research information remains available; this does not establish permanent discontinuation.
About P21
Pre-clinical / research-onlyAlso known as: P021 · CNTF-mimetic tetrapeptideP21 (also written P021) is a small tetrapeptide derived from the active region of ciliary neurotrophic factor (CNTF), developed in Khalid Iqbal's laboratory at the New York State Institute for Basic Research in Developmental Disabilities as an orally bioavailable, brain-penetrant neurogenic agent for Alzheimer's disease.[1]
P21 mimics the neurogenic, but not the pro-inflammatory or cachexia-inducing, activity of CNTF. Iqbal's group reports that P21 enhances hippocampal neurogenesis, increases BDNF expression, and inhibits leukaemia inhibitory factor (LIF) signalling, producing a dissociated neurotrophic profile not seen with CNTF itself.[2]
Pre-clinical work in 3xTg-AD, Alzheimer's, Down syndrome, and traumatic-brain-injury mouse models has reported rescued cognitive performance, reduced tau hyperphosphorylation, and increased adult hippocampal neurogenesis.[2][3] No registered human clinical trial has been conducted.
Regulatory: Not FDA-approved. No registered human clinical trial. Research peptide only.
P21: Mechanisms, Half-Life & Research Data
A skimmable deep dive into how P21 works and what it is being studied for — tied back to what size to buy. Detailed debates and community notes are tucked into the expandable panels below. All citations resolve to the sources list at the bottom of this page.
How it works
P21 (P021) is a small tetrapeptide engineered from the active region of ciliary neurotrophic factor (CNTF) — a member of the IL-6 cytokine family that is highly neurogenic but also induces weight loss, anorexia, and pro-inflammatory signalling when given as the full-length protein.[1] Iqbal's laboratory designed P21 specifically to retain the neurogenic and synaptotrophic activity of CNTF while losing the leukaemia inhibitory factor (LIF) signalling that drives the unwanted systemic effects, producing what the group describes as a "dissociated CNTF mimetic."[2][4] In rodents, P21 enhances dentate-gyrus neurogenesis, increases BDNF and its TrkB receptor in the hippocampus, reduces tau hyperphosphorylation, and crosses the blood-brain barrier well enough to be active after oral dosing — an unusual property for a peptide and the basis for the entire translational case.[1][2] Pre-clinical protocols typically use 60 nmol/kg/day oral dosing for several months.
Active research areas
- 3xTg-AD mouse model of Alzheimer's diseaseKazim et al. reported that chronic oral P21 rescued cognitive performance, reduced tau hyperphosphorylation, and increased adult hippocampal neurogenesis in the 3xTg triple-transgenic AD model.[2] One of the strongest signals for the molecule.
- Sporadic AD rat modelBolognin et al. used an intracerebroventricular streptozotocin sporadic-AD rat model and reported that P21 rescued cognitive impairment and reduced tau pathology.[3] Independent replication of the AD-model signal outside the originating lab.
- Aβ-driven tau aggregationKhatoon et al. characterised the mechanistic claim that oral P21 disrupts Aβ42-mediated tau aggregation, addressing the question of *how* a small CNTF-mimetic could meaningfully alter AD pathology rather than just neurogenesis.[5]
- Down syndrome and TBI rodent modelsThe Iqbal group and collaborators have extended P21 testing into Down-syndrome and traumatic-brain-injury rodent models with reported cognitive-rescue signals, broadening the proposed therapeutic surface beyond AD.[4]
Open questions & leading hypotheses (2)
- Hypothesis: P21 produces clinically meaningful cognitive benefit in human Alzheimer's disease.Evidence: The rodent AD-model record is unusually consistent for a neurotrophic peptide, with both transgenic[2] and sporadic[3] models showing cognitive rescue. Counter-evidence: no registered human clinical trial has been launched in the decade since the foundational papers,[6] and the broader history of neurotrophic-mimetic AD drugs is one of consistent failure to translate from mouse to human.
- Hypothesis: The "dissociated CNTF" claim — that P21 retains the neurogenic activity without the pro-inflammatory and cachexia-inducing effects — holds at human doses.Evidence: Iqbal-group toxicology in rodents reports no weight loss or systemic inflammation at chronic neurogenic doses.[2][4] Counter-evidence: no human safety data exist, and the receptor-level mechanism by which a small peptide cleanly separates two arms of CNTF signalling has not been characterised at the structural-biology level outside the originating group.
Sources & references (6)
Peer-reviewed literature, FDA documents, and trial registrations cited above. Vendor pricing, COA data, and live calculator statistics shown elsewhere on this page are sourced from the WPA database independently of this list.
- [1]Chohan MO et al. Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide. Neurobiol Aging 2011;32:1420–1434. · PMID: 19767127 link
- [2]Kazim SF et al. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. Neurobiol Dis 2014;71:110–130. · PMID: 25046994 link
- [3]Bolognin S et al. An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide. Acta Neuropathol 2014;127:265–278. · PMID: 24077734 link
- [4]Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener 2016;11:50. · PMID: 27400746 link
- [5]Khatoon S et al. Aβ42-mediated tau aggregation in Alzheimer's disease is rescued by an oral CNTF small peptide mimetic. Mol Psychiatry 2015;20:1–8. · PMID: 25869804 link
- [6]ClinicalTrials.gov — registry search for "P021 CNTF" returns no interventional human trials as of May 2026. link
P21 Calculator Input Observations
In lifetime P21 calculator inputs, 250mcg is the most frequent entered amount (12 of 21 runs). Calculator runs and frequency responses are different populations, not unique people or confirmed administration. Separate modal inputs do not establish a most-common joint protocol, a recommendation, or a cycle length.
About P21
P21 (also written P021) is a small tetrapeptide derived from the active region of ciliary neurotrophic factor (CNTF), developed in Khalid Iqbal's laboratory at the New York State Institute for Basic Research in Developmental Disabilities as an orally bioavailable, brain-penetrant neurogenic agent for Alzheimer's disease.
P21 is tracked under the Memory Peptides category on WPA. Its reported half-life is ~few hours (estimated). Calculator inputs do not establish why a cadence was selected or validate a protocol. Not FDA-approved.
Frequently Asked Questions: P21
Are current P21 offers available?
Current P21 vial offers are unavailable in this comparison. Research information remains available; this does not establish permanent discontinuation.
What can I check if P21 listings become available?
Check the exact compound, format, labelled quantity, named laboratory, test date, and batch match. Confirm any future listing price, discount terms, and stock directly with the vendor. Catalog COA fields alone are not independent verification.
Does research activity establish current P21 availability?
No. Search interest, calculator entries, historical prices, related compounds, and other formats do not establish current offers in this comparison. Research information and navigation to other compounds remain available.