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.

Identifiers

Synonyms: Dihexa, PNB-0408
CAS No.: 1401708-83-5
Formula / MW: C₂₇H₄₄N₄O₅ • ~504.7 g·mol⁻¹
Primary target: HGF/c-Met receptor activation (neurotrophic signalling)

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**.
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.
Because it is blood-brain-barrier permeable, it is used in models of cognitive impairment, neurodegeneration and brain-injury research.

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.
To explore **neuro-plasticity enhancement** protocols (learning/memory tasks, hippocampal connectivity).

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.
What changed: Increased synaptophysin protein levels, increased neuronal counts in hippocampus, improved spatial memory/learning versus controls.
Why it matters: Suggests that not only protecting neurons but re-wiring synapses is feasible via HGF/c-Met activation in neurodegenerative contexts.

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.
What changed: Preliminary data suggest neuro-repair/axon-rescue in models of dopaminergic neuron damage.
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.

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.
Human data extremely limited: No large, controlled human trials exist; most data are preclinical/in-vitro.
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.
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.