Chronic oral administration of the CNTF-derived peptidergic compound (P021) in triple-transgenic Alzheimer's mice improved cognition and reduced Alzheimer's-type pathology, including effects on amyloid and tau and improved synaptic plasticity.
P21

Overview
Last reviewed: 2026-08-18
Identity & Aliases
Also known as
Status: Research compound - CREB modulator
Full composition (formula, molecular weight, sequence) in Quick Facts →
Research Areas
Available Evidence
No human clinical trials of P21/P021 were found in indexed sources.
In a triple-transgenic (3xTg-AD) mouse model of Alzheimer's disease, chronic oral treatment with the CNTF-derived neurotrophic peptidergic compound P021 improved cognitive performance and exerted a disease-modifying effect on amyloid and tau pathology and synaptic plasticity.
The compound is derived from the active region of ciliary neurotrophic factor (CNTF) and is designed to mimic neurotrophic signaling (e.g., via STAT3/CREB pathways) while crossing the blood-brain barrier; cell-based studies support neurotrophic activity.
Most claims circulating in research-use markets (cognitive enhancement in healthy adults, depression, aging) are extrapolations from one Alzheimer's mouse study and are unproven in humans. Dosing, safety, and efficacy in people are entirely unknown.
Key Studies & Findings
Benefits & Effects
Enhanced neurogenesis in dentate gyrus
Increased BDNF expression
Reduced tau hyperphosphorylation
Improved synaptic plasticity
Cognitive improvement in AD models
Side Effects & Safety
Limitations & Open Questions
Pharmacology
Reported Research Dosing
Reported values from research literature and community protocols. Educational reference only — not a dosing recommendation or medical advice.
100-300mcg daily
Research Protocols
Cognitive enhancement
- Dose
- 500mcg-1mg
- Frequency
- 1x daily
- Route
- Intranasal
Acute cognitive boost
- Dose
- 1-2mg
- Frequency
- As needed
- Route
- Intranasal
Maintenance/neuroprotection
- Dose
- 500mcg
- Frequency
- 1x daily
- Route
- Intranasal
Initial assessment
- Dose
- 500mcg
- Frequency
- 1x daily
- Route
- Intranasal
Research protocols are for educational purposes only. Always consult qualified medical professionals.
Frequently Asked Questions
What is P21 derived from?
It is a CNTF (ciliary neurotrophic factor)-derived peptide designed to mimic neurotrophic signaling; it is sometimes written P021 (CAS 1246751-68-7).
Has P21 been tested in humans?
No human clinical trials were found; the only indexed efficacy data are from a triple-transgenic mouse model of Alzheimer's disease.
Is P21 approved?
No. It is an unapproved research compound with no regulatory clearance anywhere.
Research Citations
Karimian A, Ahmadi Y, Yousefi B (2016)
Shamloo B, Usluer S (2019)
Yan J, Chen S, Yi Z, Zhao R, Zhu J, Ding S, Wu J (2024)
Wang B, Wang L, Gasek NS, Zhou Y, Kim T, Guo C, Jellison ER, Haynes L, Yadav S, Tchkonia T, Kuchel GA, Kirkland JL, Xu M (2021)
Zohny SF, Al-Malki AL, Zamzami MA, Choudhry H (2019)
+ 20 more citations
Related Resources
Quick Facts
Molecular Weight
2.3
Sequence
Ac-DGGLAG-NH2
Mechanism
CREB pathway activator for memory enhancement
Safety Information
Research compound only. Very limited human safety data available.
Citations
25Karimian A, Ahmadi Y, Yousefi B (2016)
Shamloo B, Usluer S (2019)
Yan J, Chen S, Yi Z, Zhao R, Zhu J, Ding S, Wu J (2024)
Wang B, Wang L, Gasek NS, Zhou Y, Kim T, Guo C, Jellison ER, Haynes L, Yadav S, Tchkonia T, Kuchel GA, Kirkland JL, Xu M (2021)
Zohny SF, Al-Malki AL, Zamzami MA, Choudhry H (2019)
+ 20 more citations