Dihexa

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Dihexa — Brain-Repair & Synaptogenesis Peptide (Ang IV analog)

Dihexa (development code PNB‑0408) is a synthetic oligopeptide derived from Angiotensin IV (Ang IV) designed for high affinity binding to the hepatocyte growth factor (HGF) / c-Met receptor axis. It crosses the blood-brain barrier and in preclinical models has shown potent effects on synaptogenesis, neuron-survival and cognitive restoration. [oai_citation:0‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8615599/?utm_source=chatgpt.com)

Identifiers

Synonyms: Dihexa, PNB-0408
CAS No.: 1401708-83-5 [oai_citation:1‡Wikipedia](https://en.wikipedia.org/wiki/Dihexa?utm_source=chatgpt.com)
Formula / MW: C₂₇H₄₄N₄O₅ • ~504.7 g·mol⁻¹ [oai_citation:2‡Alzheimer's Drug Discovery Foundation](https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf?utm_source=chatgpt.com)
Primary target: HGF/c-Met receptor activation (neurotrophic signalling) [oai_citation:3‡ProSpec](https://www.prospecbio.com/dihexa?utm_source=chatgpt.com)

How It Works (Plain English)

Dihexa mimics HGF, binds to the c-Met receptor, and triggers downstream signalling that promotes **synapse formation**, **neuron survival** and **neural‐circuit repair**. [oai_citation:4‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8615599/?utm_source=chatgpt.com)
This means it may help convert “living but under-connected” neurons into more functional networks by increasing synaptic markers (e.g., synaptophysin) in preclinical studies. [oai_citation:5‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8615599/?utm_source=chatgpt.com)
Because it is blood-brain-barrier permeable, it is used in models of cognitive impairment, neurodegeneration and brain-injury research. [oai_citation:6‡Michael J. Fox Foundation](https://www.michaeljfox.org/grant/development-small-molecule-hepatocyte-growth-factor-mimetics-treatment-parkinsons-disease?utm_source=chatgpt.com)

Why Researchers Use It

To examine **synaptogenesis**, neural-network repair, and cognitive restoration in rodent/neuro models.
To study **neurodegenerative disease models** (e.g., Alzheimer’s, Parkinson’s) through a HGF/c-Met repair axis. [oai_citation:7‡Michael J. Fox Foundation](https://www.michaeljfox.org/grant/development-small-molecule-hepatocyte-growth-factor-mimetics-treatment-parkinsons-disease?utm_source=chatgpt.com)
To explore **neuro-plasticity enhancement** protocols (learning/memory tasks, hippocampal connectivity). [oai_citation:8‡Creative Peptides](https://www.creative-peptides.com/resources/what-is-dihexa-peptide.html?utm_source=chatgpt.com)

Key Study Themes — What Was Tested, What Changed, Why It Matters

Synaptic & cognitive restoration in Alzheimer’s-models

What was tested: In transgenic APP/PS1 mice and aged/chemically induced cognitive-impairment models, Dihexa administered and endpoints included synaptophysin expression, neuron counts, spatial memory. [oai_citation:9‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8615599/?utm_source=chatgpt.com)
What changed: Increased synaptophysin protein levels, increased neuronal counts in hippocampus, improved spatial memory/learning versus controls. [oai_citation:10‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8615599/?utm_source=chatgpt.com)
Why it matters: Suggests that not only protecting neurons but re-wiring synapses is feasible via HGF/c-Met activation in neurodegenerative contexts. [oai_citation:11‡Alzheimer's Drug Discovery Foundation](https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf?utm_source=chatgpt.com)

Motor-neuron / Parkinson’s-Risk Models via HGF mimetic

What was tested: Small-molecule HGF mimetic in Parkinson’s-style rodent models, looking at motor neuron survival and functional recovery. [oai_citation:12‡Michael J. Fox Foundation](https://www.michaeljfox.org/grant/development-small-molecule-hepatocyte-growth-factor-mimetics-treatment-parkinsons-disease?utm_source=chatgpt.com)
What changed: Preliminary data suggest neuro-repair/axon-rescue in models of dopaminergic neuron damage. [oai_citation:13‡Michael J. Fox Foundation](https://www.michaeljfox.org/grant/development-small-molecule-hepatocyte-growth-factor-mimetics-treatment-parkinsons-disease?utm_source=chatgpt.com)
Why it matters: Indicates a broader axis of repair beyond cognitive memory circuits (toward motor-neuron resilience).

Potential Research Applications

Neuro-degeneration & Aging

Alzheimer’s, Parkinson’s, age-related synaptic decline, mild cognitive impairment.

Cognitive Enhancement / Brain Repair

Learning/memory enhancement, hippocampal plasticity, post-concussion repair.

Neural Network Remodelling

Synaptogenesis assays, dendritic spine density, neural stem-cell reactivation under HGF/c-Met signalling.

Synergistic / Comparator Peptides

Selank / Semax

Why pair: These peptides modulate neuro-immune and neuro-trophic axes—pairing with Dihexa’s repair axis offers layered brain-repair protocols.

MOTS-c / SS-31

Why pair: Mitochondrial support peptides combined with synaptic-repair peptides may offer enhanced neuro-resilience research designs.

Brain-Derived Neurotrophic Factor (BDNF) mimetics / HGF analogues

Why compare: Dihexa is reported to be several orders of magnitude more potent than BDNF in synaptic assays. [oai_citation:14‡Wikipedia](https://en.wikipedia.org/wiki/Dihexa?utm_source=chatgpt.com)

Known Concerns (Context)

Tumorigenic risk via c-Met activation: The HGF/c-Met pathway is a known oncogenic pathway—long-term safety data are lacking. [oai_citation:15‡Alzheimer's Drug Discovery Foundation](https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf?utm_source=chatgpt.com)
Human data extremely limited: No large, controlled human trials exist; most data are preclinical/in-vitro. [oai_citation:16‡Alzheimer's Drug Discovery Foundation](https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf?utm_source=chatgpt.com)
Mechanistic breadth: Because it drives growth/repair cascades, off-target effects and compensatory responses are possible—monitor broad endpoints in research models.
General: For laboratory research use only; not for human consumption or therapeutic use.

Specifications & Handling

Form: Lyophilized peptide powder (lot-coded) or solid (depending on supplier)
Purity: Typically ≥98 % (HPLC/MS verified) in research-grade batches. [oai_citation:17‡Selleck Chemicals](https://www.selleckchem.com/products/dihexa.html?utm_source=chatgpt.com)
Storage: ≤ −20 °C; protect from light/moisture; handle as per peptide-storage best practices.

In solution: Reconstitute fresh; document vehicle, concentration, pH and time to assay.
Labeling: Tamper-evident; “research use only”; traceable lot/SKU and expiration.

Regulatory & Use Notice

Sold for laboratory research use only. Not for human consumption, medical, or veterinary use. No human-use instructions are provided. Buyer is responsible for safe handling and regulatory and ethical compliance.

Dihexa Peptide Research | Synaptogenesis & Brain Repair | Neurodegeneration & Cognitive Enhancement Studies

Keywords: Dihexa, PNB-0408, angiotensin IV analog, HGF/c-Met agonist peptide, synaptogenesis, cognitive repair, Alzheimer’s model, Base Peptides.

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Instructions are NOT provided before or after purchase.

Peptide molecules are unfinished and require reconstitution from a skilled and licensed professional to activate the compound into liquid form. Instructions are not provided for reconstitution, dosing, or adminstration. All products are strictly intended for research purposes and laboratory experimentation. Handling should be by skilled licensed and credentialed professionals only. Non experimental use is strictly prohibited.

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