Emerging Research

P21 (P021)

Cognitive & Neurological · ['P021', 'Peptide 021', 'GLXC-21260', 'Ac-DGGLAG-NH2']

A small ciliary neurotrophic factor (CNTF)-derived peptide mimetic with an adamantylated residue for blood-brain-barrier penetration, studied in Alzheimer's-model animals for neurogenesis, BDNF induction, and reduction of tau and amyloid pathology.

🔬 Research use only — not for human or veterinary use. K4 Elite does not provide dosing instructions.

Molecular Formula

C27H42N6O8

Molecular Weight

578.7 g/mol

PubChem

CID 56589645 ↗

Research Level

Emerging Research

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P021 (also written P21, Peptide 021, GLXC-21260) is a small peptidergic compound derived from the biologically active region of human ciliary neurotrophic factor (CNTF, residues 148-151) by epitope mapping. An adamantane-based residue is added at the C-terminus (giving Ac-DGGL(A)G-NH2) to increase lipophilicity, improve blood-brain-barrier permeability, and reduce degradation by exopeptidases.

It was developed in the laboratory of Khalid Iqbal and colleagues and has been characterized in multiple Alzheimer's-disease animal models. PubChem lists it under CID 56589645 with molecular formula C27H42N6O8 and a molecular weight near 578.7 g/mol.

All findings described here are from preclinical animal and cell research. There are no established human treatment outcomes, and this entry is provided for research and reference use only.

P021 is described in the literature as a neurogenic and neurotrophic compound. Proposed mechanisms include inhibition of leukemia inhibitory factor (LIF) signaling and enhancement of dentate-gyrus neurogenesis, together with increased expression of brain-derived neurotrophic factor (BDNF).

Through increased BDNF signaling, animal studies report a decrease in the activity of glycogen synthase kinase-3beta (GSK-3beta), a major tau kinase, which is associated in these models with reduced abnormal tau hyperphosphorylation and attenuated amyloid-beta and neurofibrillary pathology.

Adult hippocampal neurogenesis: Rodent studies reporting enhanced dentate-gyrus neurogenesis and synaptic markers.
BDNF induction: Animal work linking P021 to increased BDNF expression and downstream GSK-3beta modulation.
Tau pathology: Studies in 3xTg-AD and related mouse models reporting reduced abnormal tau hyperphosphorylation.
Amyloid-beta pathology: Reports of decreased Abeta plaque load in aged transgenic mice.
Cognition and behavior: Memory and learning endpoints in Alzheimer's-model mice.
Developmental / early-life treatment: Studies of prenatal-to-early-postnatal neurotrophic treatment preventing Alzheimer-like pathology in mouse models.

📋 How published studies were conducted — a research reference summarizing study designs from the literature. This is not usage, dosing, or administration guidance. K4 Elite does not provide dosing instructions; determining any research protocol is the sole responsibility of the qualified researcher.

Kazim et al., prevention of dendritic and synaptic deficits (J Neurosci / PMC5488423): Reported that chronic P021 treatment in a mouse model was associated with prevention of synaptic and neurogenesis deficits and cognitive impairment. Reported for reference only.

3xTg-AD cognition and pathology studies: Work in the 3xTg-AD mouse model reported rescue of cognitive deficits at 4 months and reduced tau hyperphosphorylation and Abeta plaque load at later timepoints. These are animal-model observations; any dosing figures are experimental parameters, not recommendations.

Prenatal-to-postnatal neurotrophic treatment study (PMC7450938): Reported that early neurotrophic treatment with P021 prevented Alzheimer-like behavior and pathology in mice. Described for information only.

Combinations examined in the research literature. Descriptive only — not a recommendation to combine compounds.

BDNF / TrkB pathway agentsSynergistic

P021's proposed action converges on BDNF signaling, so BDNF-pathway tool compounds share a common node in research contexts.

GSK-3beta inhibitorsSynergistic

Both are associated with reduced tau kinase activity in models; a theoretical mechanistic overlap.

CNTF and other neurotrophic mimeticsCompatible

Related class of small-molecule neurotrophic mimetics used as comparators.

LIF-signaling activatorsCaution

P021 is described as inhibiting LIF signaling, so LIF activators could theoretically oppose part of its proposed mechanism.

References are being compiled for this entry.

What is P021 derived from?

It is a small peptide mimetic derived from the active region of ciliary neurotrophic factor (CNTF, residues 148-151), with an adamantylated C-terminal residue added to aid brain penetration and stability.

What does P021 do in Alzheimer's models?

Animal studies report enhanced neurogenesis, increased BDNF, reduced GSK-3beta activity, and lower tau and amyloid-beta pathology, associated with improved cognitive endpoints.

Why is an adamantane residue attached?

The adamantane-based residue increases lipophilicity to improve blood-brain-barrier permeability and reduces breakdown by exopeptidases in the research literature.

Is P021 the same as P21 the protein?

No. Despite the similar label, this P021 is a synthetic CNTF-derived neurotrophic peptide mimetic and is unrelated to the cyclin-dependent kinase inhibitor protein p21.

Is P021 available for personal or clinical use?

No. P021 is a research-use-only compound with data limited to preclinical models. It is not approved for human use, and nothing here is medical advice or a usage recommendation.

Disclaimer: This profile summarizes published preclinical and laboratory research for reference only. It is not medical advice and makes no claim of safety or efficacy in humans. Determining any research protocol is the sole responsibility of the qualified researcher. Products are sold strictly for in-vitro research and have not been evaluated by the FDA.