# P21

> Evidence tier C — Animal data · Mind · reviewed 2026-11-08
> Source page: https://peptidemeta.com/p/p21/

Also known as: P021, Peptide 021, Ac-DGGLAG-NH2

## Quick answers

**What is P21?**

A synthetic peptide derived from an active region of ciliary neurotrophic factor (CNTF), with an adamantane-modified C-terminus (Ac-DGGL-[adamantylglycine]-NH2, also called P021).

**How strong is the evidence for P21?**

Tier C (animal data) on the peptidemeta evidence scale. Evidence is limited to mouse and rat studies from the developing laboratory (e.g. Li et al., FEBS Lett 2010); no published human studies.

**Is P21 FDA-approved?**

No. P21 is not approved by the FDA for any use.

**Is P21 banned in sport?**

Yes. P21 is prohibited in sport by the World Anti-Doping Agency under S0 (non-approved substances).

**How does P21 work?**

P21 (P021) is a CNTF-derived peptidergic compound. In mouse studies it increased brain-derived neurotrophic factor (BDNF) expression and decreased glycogen synthase kinase-3 beta (GSK-3β) activity, which was associated with reduced tau hyperphosphorylation and increased hippocampal neurogenesis and synaptic plasticity.

**What is known about the safety of P21?**

No human safety data. Only preclinical animal studies available.

## Key facts

- **Evidence tier:** C (Animal data)
- **FDA:** not approved
- **WADA:** prohibited (S0)
- **Peptide:** yes
- **Sequence:** [Ac]DGGL[AdaG][NH2] (5 residues)
- **Formula:** C27H42N6O8
- **Molecular weight:** 578.7 g/mol
- **Discovered:** 2010 — Designed from a CNTF-derived peptide at the NYS Institute for Basic Research (Li et al., FEBS Lett 2010).
- **Routes studied:** Intranasal, Subcutaneous

## Overview

A synthetic peptide derived from an active region of ciliary neurotrophic factor (CNTF), with an adamantane-modified C-terminus (Ac-DGGL-[adamantylglycine]-NH2, also called P021). Explored in mouse and rat models for neurogenesis and Alzheimer-related decline.

## Mechanism

P21 (P021) is a CNTF-derived peptidergic compound. In mouse studies it increased brain-derived neurotrophic factor (BDNF) expression and decreased glycogen synthase kinase-3 beta (GSK-3β) activity, which was associated with reduced tau hyperphosphorylation and increased hippocampal neurogenesis and synaptic plasticity.

## Effects reported in research

_Reported outcomes, not promises; see the evidence tier._

- Promoted hippocampal neurogenesis
- Improved spatial learning and memory
- Reduced tau hyperphosphorylation
- Enhanced dendritic complexity

## Safety & unknowns

No human safety data. Only preclinical animal studies available. Mechanism of promoting neurogenesis carries unknown long-term risks. Not FDA-approved. Data limited to rodent studies.

## Studies

- Kazim SF, Blanchard J, Dai CL, et al. (2014). *Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease*. Neurobiology of Disease. Preclinical. https://pubmed.ncbi.nlm.nih.gov/25046994/
  Twelve months of oral P021 in 3xTg-AD mice reduced tau hyperphosphorylation and soluble Aβ, increased BDNF and decreased GSK-3β activity, and rescued deficits in cognition, neurogenesis, and synaptic plasticity.

## Status sources

- [PubChem CID 56589645 — Peptide 021](https://pubchem.ncbi.nlm.nih.gov/compound/56589645)
- [Li et al., FEBS Lett 2010 (design, mouse studies)](https://pubmed.ncbi.nlm.nih.gov/20600002/)
- [Kazim et al., Neurobiol Dis 2014 (3xTg-AD mouse study)](https://pubmed.ncbi.nlm.nih.gov/25046994/)
- [WADA Prohibited List 2026 (S0)](https://www.wada-ama.org/en/resources/world-anti-doping-code-and-international-standards/prohibited-list)

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Educational reference only — not medical advice. No dosing information is published. Tiers rate the strength of published evidence, not effectiveness or safety.