P021
P021 (Peptide 021) is an orally active, blood-brain barrier penetrant neurotrophic/neurogenic pentapeptide derived from the most active region of ciliary neurotrophic factor (CNTF). P021 competitively inhibits leukemia inhibitory factor (LIF) and promotes BDNF transcription. P021 targets neurogenesis and synaptic plasticity. P021 prevents neurodegeneration, Amyloid-β pathology, tau protein pathology and cognitive deficits, rescues episodic memory impairment and reduces mortality in 3xTg-AD mice. P021 is applicable to the research of Alzheimer's disease.
For research use only. We do not sell to patients.
- CAS No.: 1246751-68-7
- Formula: C27H42N6O8
- Molecular Weight:578.66
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
Parmacokinetics
| Species | Dose | Route | T1/2 |
|---|---|---|---|
| Mice[1] | 162 nM | p.o. | >3 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:3xTg-AD (female, 3 months old at study initiation, hybrid 129/Sv x C57BL/6 genetic background, Alzheimer's disease transgenic model harboring APP_Swe, tau P301L, and PS1 M146V knock-in mutations)[1]
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Dosage:60 nM P021/g feed (equivalent to ~162 nM P021/mouse/day)
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Administration:p.o.; continuously; 18 months
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Result:Prevented neurodegeneration (measured by Fluorojade C staining percent area) in CA3, dentate gyrus, parietal cortex, and frontal cortex at 9 months post-treatment relative to vehicle-treated mice.
Prevented neurodegeneration in CA1, CA3, DG, and parietal cortex at 18 months post-treatment relative to vehicle-treated mice.
Reduced Aβ plaque load (percent area occupied by 4G8 staining) in the subiculum at 9 months post-treatment relative to vehicle-treated mice, with no significant effect in CA1.
Reduced Aβ load in the subiculum at 15 months post-treatment relative to vehicle-treated mice, with no effect in CA1.
Reduced Aβ load in both CA1 and subiculum at 18 months post-treatment relative to vehicle-treated mice.
Slowed Aβ load increase over time in the subiculum via regression analysis.
Reduced tau hyperphosphorylation (PHF1 staining percent area) in CA1 and subiculum, with a trend toward reduction in AT8 staining in CA1 at 9 months post-treatment relative to vehicle-treated mice.
Reduced AT8 staining in CA1 and subiculum, and reduced PHF1 staining in CA1 and subiculum at 15 months post-treatment relative to vehicle-treated mice.
Reduced AT8 staining in CA1 and subiculum, reduced PHF1 staining in CA1 and subiculum, and reduced hippocampal PHF1-positive tau on western blot at 18 months post-treatment relative to vehicle-treated mice.
Slowed the increase in AT8 and PHF1 staining over time in CA1 and subiculum via regression analysis.
Rescued episodic memory impairment in the Novel Object Recognition task at 16-17 months post-treatment, with treated mice showing a significantly higher discrimination index relative to vehicle-treated mice.
Increased survival rate from 41% (vehicle) to 87% by week 71 of treatment, and reduced hindlimb paralysis incidence (1/32 vs 5/34 vehicle-treated mice).
Chemical Information
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CAS No. 1246751-68-7
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Molecular Weight 578.66
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Formula C27H42N6O8
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SMILES
OC(C[C@H](NC(C)=O)C(NCC(NCC(N[C@@H](CC(C)C)C(NC12CC3(CC(CC(C3)C2)C1)C(N)=O)=O)=O)=O)=O)=O
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Synonyms
Peptide 021
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Sequence
Ac-Asp-Gly-Gly-Leu-{Gly(adamantane)}
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Sequence Shortening
Ac-DGGL-{Gly(adamantane)}
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Neurotoxicity Study
This protocol assesses in vitro neurotoxicity by combining neuronal viability, mitochondrial/metabolic activity, neurite outgrowth, and optional neuronal network function readouts. Calcein-AM or resazurin/PrestoBlue readouts estimate viable or metabolically active cells; βIII-tubulin immunofluorescence detects neuronal morphology and neurite networks; TMRE detects mitochondrial membrane potential; and MEA recordings detect functional changes in neuronal network activity.
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SH-SY5Y neuronal-like differentiation
SH-SY5Y neuronal-like differentiation uses defined culture conditions to shift proliferative human neuroblastoma cells toward a neuron-like state, mainly assessed by reduced proliferation, neurite extension, neuronal-marker expression, and, in some protocols, increased dependence on neurotrophic support. Retinoic acid (RA) is commonly used for the first differentiation phase, and sequential RA followed by brain-derived neurotrophic factor (BDNF) in serum-free medium is a well-characterized approach for generating neuron-like SH-SY5Y cultures with extensive neurite outgrowth. The primary readouts are morphology-based neurite outgrowth and marker-based confirmation using proteins such as βIII-tubulin, MAP2, GAP43, synaptophysin, NeuN, NSE, TH, or related neuronal/synaptic markers, depending on the study endpoint.
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Cell differentiation
Cell differentiation refers to the process in which cells of the same origin gradually produce cell groups with different morphological structure and functional characteristics.
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)