P21
Also known as: P021, CNTF-derived peptidergic compound
P21 is a CNTF-derived peptide that increases BDNF expression, competitively inhibits leukemia inhibitory factor signaling, raises phosphorylated CREB and lowers GSK-3 beta activity to promote dentate gyrus neurogenesis and synaptic plasticity in animal models.
- Drug class
- CNTF-derived neurotrophic peptide mimetic
- Primary targets
- CNTF signaling pathway, Leukemia inhibitory factor (LIF), BDNF/TrkB, CREB, GSK-3 beta
- Dose reference
- No established human dose; preclinical rodent studies used roughly 60 nmol/g of feed orally (about 162 nmol/mouse/day) - not a human recommendation.
- Half-life
- Not established in humans; preclinical reports describe plasma stability exceeding 3 hours and high gastric/intestinal stability.
- Developer / origin
- Khalid Iqbal and colleagues, New York State Institute for Basic Research in Developmental Disabilities
- Reference year
- 2010
- Evidence score
- 2/5 - Preclinical only (animal evidence, no human trials)
Preclinical only (animal evidence, no human trials)
P21 (P021) has a coherent and internally consistent preclinical record in rodent Alzheimer's and aging models, including increased BDNF, hippocampal neurogenesis, reduced tau pathology and improved cognition. However, the evidence is almost entirely from one research lineage, there are no completed human clinical trials, no approvals and no validated human dose, so confidence for human use is low.
Mostly animal, ex vivo, cell, or indirect evidence.
Evidence basis
- 2010 FEBS Letters (Li et al.) introducing adamantane-modified CNTF peptides showing improved learning, neurogenesis and synaptic plasticity in mice
- 2014 Neurobiology of Disease (Kazim et al.) chronic oral P021 reducing tau pathology and improving cognition in 3xTg-AD mice
- 2017 Alzheimer's Research & Therapy (Baazaoui & Iqbal) rescuing dendritic/synaptic deficits in transgenic AD mice
- Absence of any registered or completed human clinical trial and no regulatory approval
Key references
- PubMedNeurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice (FEBS Lett. 2010)
- PubMedDisease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease (Neurobiol Dis. 2014)
- PMCPrevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound (Alzheimers Res Ther. 2017)
How to read this entry
Dose references and half-life values are pulled from trial protocols, labels, reviews, or published summaries where available. They are context for research and comparison, not a personal dosing recommendation.
Status matters: approved drugs have regulated indications; investigational compounds are still being studied; research-only peptides do not have established human dosing, safety, or efficacy for consumer use.
P21 guides
Read the matching guide or adjacent research pages for more context.
Peptide calculators
Use calculators for concentration, unit conversion and repeated-dose accumulation math.
Compare with related peptides
Stay inside the same research category and compare mechanism, status and evidence quality.
Selank
TP-7
Russian-developed analog of tuftsin marketed (in Russia) as an anxiolytic. Mechanism involves modulation of GABA and stress-response pathways.
Semax
ACTH(4-10) analog
Heptapeptide derived from ACTH(4-10). Russian neuropeptide studied for nootropic and neuroprotective effects, partly via BDNF upregulation.
Cortexin
polypeptide cortical fraction
Cortexin is a low-molecular-weight polypeptide fraction from animal cerebral cortex proposed to act as a multi-target neuroprotectant by modulating glutamate (AMPA, kainate, mGluR) and GABA-A receptors, inhibiting brain caspase-8, and influencing neurotrophic and antioxidant pathways.
N-Acetyl Semax
N-Acetyl Semax Amidate, NA Semax
It is a chemically stabilized analog of the ACTH(4-7)-derived peptide Semax that, in preclinical models, binds specifically in brain tissue and raises BDNF and other neurotrophins while modulating ischemia-related inflammatory and neurotransmitter gene expression.
Category hub
Open the category page for the full comparison table and FAQ.