Product Usage: This PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. All product information available on this website is for educational purposes only. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals. This product is not a drug, food, or cosmetic and may not be misbranded, misused or mislabeled as a drug, food or cosmetic.

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P21 5mg

Name: P21 5mg
SKU: P21-5MG
Availability: OutOfStock

$60.00

≥99% purity · HPLC verified · MS confirmed How we test →

Summary Description: P21 is a small peptide compound designed to mimic the effects of ciliary neurotrophic factor (CNTF), a natural protein that supports the growth and survival of brain cells. P21 works through two complementary mechanisms: it blocks a signal that holds brain stem cells in a dormant state, and it boosts levels of brain-derived neurotrophic factor (BDNF), a key protein that helps new neurons survive, mature, and form connections. Unlike the full-length CNTF protein, which cannot penetrate the brain, P21 crosses the blood–brain barrier and has shown no adverse effects in preclinical studies up to one year of treatment. In animal models of Alzheimer’s disease, cognitive aging, and Down syndrome, P21 has been shown to restore memory, promote neurogenesis, repair damaged synapses, and reduce the tau and amyloid-? protein accumulations that characterize Alzheimer’s disease^1-5.

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COMPOUND NAME

P21

SYNONYMS

Peptide 021 (P021; Compound 021), Ac-dggl-adamatanylglycine-NH2

CAS NUMBER

1246751-68-7

MOLECULAR FORMULA

C₂₇H₄₂N₆O₈

MOLECULAR WEIGHT

578.3 g/mol

STRUCTURE

CNTF tetrapeptide derivative

PEPTIDE SEQUENCE

Ac-DGGLAG-NH?

CHEMICAL STRUCTURE

Molecular Formula: C₂₇H₄₂N₆O₈

Source: PubChem

P21 mimics CNTF activity by helping activate the brain’s own repair and growth pathways. It blocks leukemia inhibitory factor (LIF) signaling, which can keep neural stem cells inactive, allowing those cells to divide and form new neurons. P21 also increases BDNF levels and enhances TrkB receptor signaling. This helps regulate GSK-3?, an enzyme linked to both tau abnormalities and amyloid-? production in Alzheimer’s disease. By reducing GSK-3? activity, P21 may help lower Alzheimer’s-related pathology while supporting synaptic function, memory-related signaling, and healthy neuronal communication^1-5.

P21 supports brain health by promoting the growth of new neurons in the hippocampus, increasing BDNF levels, and helping restore key signaling pathways involved in memory and learning. It reduces GSK-3? activity, which may help decrease accumulation of toxic protein species, while also supporting the repair of damaged dendrites and synapses. P21 has been shown in animal models of Alzheimer’s disease, aging, and Down syndrome to improve learning and memory, restore NMDA and AMPA receptor function, reactivate CREB signaling, and reduce myo-inositol, a marker associated with brain inflammation and glial scarring^1-5.

Store at 2-8°C. For long-term storage, keep at -20°C. Protect from light and moisture.

Amino Acids, Peptides, and Proteins; Neurotrophic Factor Mimetics

N/A

Property

Description

CAS Number

1246751-68-7

Molecular Formula

C27H42N6O8

Molecular Weight (MW)

578.3 g/mol

Mechanism of Action

CNTF peptide mimetic, blocks LIF signaling and helps increase BDNF activity

Biological Activity

Promotes new neuron growth, supports synaptic repair, increases BDNF levels, restores learning and memory in preclinical models of Alzheimer’s disease, aging, and Down syndrome

Supplied Form

Lyophilized powder

Purity

>99% (HPLC)

Storage

2-8°C (short-term); -20°C (long-term). Keep dry and protected from light.

Drug Categories

Amino Acids, Peptides, and Proteins; Neurotrophic Factor Mimetic

Additional Notes

P21 crosses the blood–brain barrier and has shown no CNTF-like adverse effects in preclinical studies.

For Research Use Only. Not intended for human or veterinary use. This compound is supplied solely for laboratory and R&D purposes.

P21 is a brain-focused peptide designed to support healthy cognitive aging by promoting the growth, survival, and connectivity of neurons. Derived from the active region of human ciliary neurotrophic factor (CNTF), P21 has been modified with an adamantylated glycine group to help it cross the blood–brain barrier and resist enzymatic breakdown^2,5,4. This makes it a more practical alternative to full-length CNTF, which has poor brain penetration and is associated with significant side effects. P21 works through two complementary pathways that may help maintain youthful brain function. First, it supports the growth of new neurons in the hippocampus by blocking LIF signaling, a pathway that can keep neural stem cells dormant^2,4,5. Second, it increases brain-derived neurotrophic factor (BDNF), a key protein involved in neuron survival, synaptic repair, learning, and memory. In multiple preclinical models, P21 restored BDNF levels in the hippocampus and cortex to or above those seen in age-matched controls^1,2,5. P21 also shows potential to protect against age-related neurodegenerative changes. By increasing BDNF activity, it helps regulate GSK-3?, an enzyme linked to tau buildup and amyloid-? production, two major features associated with Alzheimer’s pathology². Through this pathway, P21 has been shown to reduce tau pathology, lower soluble amyloid-? levels, support synaptic health, and improve learning and memory outcomes in preclinical animal models. These findings make P21 a promising research compound for studying brain repair, cognitive resilience, and healthy aging.

Cognitive Aging: In aged Fisher rats, roughly comparable to 65-year-old humans, P21 given daily for about 3 months significantly improved learning and memory¹.

Alzheimer’s Disease: In 3×Tg-AD mice, P21 given before overt pathology and continued for up to 18 months preserved dendritic and synaptic structure, enhanced neurogenesis, and improved spatial and short-term memory⁴.

Neurogenesis: Across multiple disease models, P21 increased hippocampal neurogenesis markers, including Ki-67+ proliferating cells and DCX+ immature neurons in the dentate gyrus^1,3,4.

Frees dormant stem cells: P21 competitively inhibits LIF binding to the CNTFR?/LIFR/gp130 receptor complex, helping release neural stem cells from dormancy so they can divide and form new neurons. This effect is supported by dose-dependent reductions in STAT3 phosphorylation^2,5.
Promotes hippocampal neurogenesis: By reducing LIF-mediated stem cell quiescence, P21 increases dividing cells and newly born, maturing neurons in the dentate gyrus, a key region for learning and memory^2,4.
Supports the brain’s repair response: P21 may strengthen the brain’s natural repair process by providing neurotrophic support needed for neurogenesis and synaptic renewal, especially in early Alzheimer’s models⁴.

Raises BDNF levels: P21 increases BDNF gene expression and protein production in the hippocampus and cortex, restoring levels to or above age-matched controls in disease models^1,2,5.
Enhances TrkB signaling: P21 upregulates full-length TrkB receptor expression, helping the brain respond more effectively to BDNF’s growth and repair signals¹.
Reactivates CREB signaling: P21 restores CREB phosphorylation, helping activate memory-related genes such as c-fos, zif268, and BDNF itself^1,4,5.
Rebuilds brain connections: Through BDNF-driven synaptic plasticity, P21 increases key synaptic and dendritic proteins, including synaptophysin, synapsin I, PSD-95, and MAP2, supporting healthier brain-circuit architecture^1,4.

Reduces tau pathology: By lowering GSK3? activity, P21 reduces abnormal tau hyperphosphorylation at both moderate and severe disease stages in 3xTg-AD mice².
Lowers amyloid-? production: P21 reduces amyloidogenic APP processing, leading to significant decreases in soluble amyloid-? levels².
Restores glutamate receptor expression: P21 helps restore NMDA and AMPA receptor subunits involved in synaptic plasticity, neuronal communication, and hippocampal-dependent memory¹.

Route of Administration

Subcutaneous

Dosing Frequency

Daily

Half-Life

3 hours

Route of Administration: subcutaneous injection (in research settings)
Dosing Frequency: Daily
Half-Life: >3 hours in plasma (some studies report >6 hours)
Formulation: Lyophilized powder

Reconstitute with sterile water or buffer as required.
Solutions should be prepared fresh and protected from light.
Avoid repeated freeze-thaw cycles.
Handle with appropriate personal protective equipment (PPE) in a well-ventilated area.

P21 is a research-grade compound that has been studied in preclinical animal models but has not undergone full clinical development. It is not approved for therapeutic use in humans, and no large-scale clinical trials have been conducted to evaluate its safety or efficacy as a medication at this time.

Bolognin, S., Buffelli, M., Puoliväli, J. & Iqbal, K. Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound. Neurobiol. Aging 35, 2134–2146 (2014).

Iqbal, K. et al. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease. Mol. Neurodegeneration 11, 50 (2016).

Costa, A. et al. Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder. Mol. Neurodev. (2024).

Baazaoui, N. & Iqbal, K. Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound. Alzheimers Res. Ther. 9, 45 (2017).

Stagni, F. et al. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome. Sci. Rep. 7, 45561 (2017).

This product is synthesized via solid-phase peptide synthesis (SPPS) and tested to ≥99% purity by HPLC with identity confirmed by mass spectrometry. A Certificate of Analysis (COA) is available for every batch. Learn about our full quality and testing process →