P21

P21 (P021, Peptide 021) is a small peptidergic compound derived from ciliary neurotrophic factor (CNTF) and built around the sequence Asp-Gly-Gly-Leu with an adamantane-containing C-terminal unit. Studies of the P21 peptide have examined dentate gyrus neurogenesis and memory tasks in adult mice, BDNF expression and synaptic markers in aged Fisher rats, tau phosphorylation in 3xTg-AD transgenic mice and tau levels in rat cerebrospinal fluid. Research Market supplies P21 as a lyophilized research reagent, with purity and identity data for each lot reported on its certificate of analysis. It is sold strictly for laboratory research use.

Chemical structure and identification

• Molecular formula: C₂₇H₄₂N₆O₈
• Molecular weight: 578.7 g/mol
• CAS number: 1246751-68-7
• PubChem CID: 56599151
• Structure: N-acetyl-L-α-aspartylglycylglycyl-N-[3-(aminocarbonyl)tricyclo[3.3.1.1^3,7]dec-1-yl]-L-leucinamide (PubChem); written in the literature as Ac-DGGL^AG-NH₂
• Synonyms: P-21; P021; Peptide 021
• Form: Lyophilized powder
• Analytical methods: RP-HPLC for purity and mass spectrometry for identity, reported on the batch certificate of analysis

Research applications

• Neurogenesis in adult mice: Given peripherally to normal adult C57Bl6 mice, P21 was associated with better learning and short-term and spatial reference memory, and with more neurogenesis and maturation of new neurons in the dentate gyrus [1]
• Cognitive aging in rats: In 22- to 24-month-old Fisher rats, chronic P21 treatment reduced age-dependent decline in learning and memory, increased BDNF expression, restored synaptic markers in cortex and hippocampus and lowered hippocampal myoinositol on MR spectroscopy [2]
• Tau and amyloid pathology: In 3xTg-AD mice treated for 12 months, P21 reduced tau hyperphosphorylation at AD-associated sites and soluble Aβ levels, changes linked to higher BDNF and lower GSK-3β activity [3]
• Cerebrospinal fluid tau: P21 crossed the blood-brain barrier in aged rats and reduced brain total tau and CSF tau, but not CSF Aβ/AβPP, toward young-adult levels [4]
• Neurotrophic mimetics: Reviewed among small-molecule neurotrophic factor mimetics, with a summary of P021 studies on LIF signaling inhibition and BDNF expression [5]

Reference citations

1. Li B. et al. (2010). Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett, 584(15):3359–3365. PMID 20600002 · DOI
2. Bolognin S. et al. (2014). Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound. Neurobiol Aging, 35(9):2134–2146. PMID 24702821 · DOI
3. Kazim S.F. 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. Neurobiol Dis, 71:110–130. PMID 25046994 · DOI
4. Khatoon S. et al. (2015). Elevated tau level in aged rat cerebrospinal fluid reduced by treatment with a neurotrophic compound. J Alzheimers Dis, 47(3):557–564. PMID 26401692 · DOI
5. Kazim S.F. and Iqbal K. (2016). Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease. Mol Neurodegener, 11(1):50. PMID 27400746 · DOI

Compound data from PubChem CID 56599151. Literature summaries describe published preclinical research and are not claims about this product’s effects in humans or animals.