Also known as: PNB-0408 · N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide
Dihexa is a potent peptidomimetic derived from angiotensin IV that acts as a superagonist of the HGF/MET signaling system. It has demonstrated cognitive-enhancing effects up to 7 orders of magnitude more potent than BDNF in rodent models of Alzheimer's disease, making it one of the most powerful pro-cognitive compounds under investigation.
Dihexa was developed at Washington State University by Joseph Harding and Joseph Wright, published in 2013. It is a small, orally bioavailable peptidomimetic built on the angiotensin IV (Ang IV) scaffold, modified to resist peptidase degradation and enhance CNS penetration. Its primary mechanism — potentiation of HGF/MET signaling — is distinct from all other nootropic peptides.
In animal models of Alzheimer's dementia, Dihexa reversed cognitive impairment at doses 10 million times lower than BDNF, the gold standard benchmark. It promotes synaptogenesis (new synapse formation) rather than merely protecting existing synapses, making it theoretically capable of structural cognitive restoration rather than just preservation.
Dihexa potentiates the binding of Hepatocyte Growth Factor (HGF) to its receptor c-MET, a receptor tyrosine kinase expressed broadly in neurons. HGF/MET signaling drives synaptogenesis, dendritic arborization, and neuronal survival — processes that are deficient in Alzheimer's disease and cognitive aging.
By amplifying HGF/MET downstream signaling (PI3K/Akt and MAPK/ERK), Dihexa significantly increases synaptic density in the hippocampus and prefrontal cortex — areas critical for memory formation and executive function. This structural remodeling is detectable by electron microscopy in treated animals.
Dihexa is one of the most potent synthetic nootropics in preclinical research — ~10 million-fold more potent than BDNF for synaptogenesis in hippocampal neurons (in vitro assay). Its effects appear to persist beyond drug elimination, suggesting structural synaptic remodelling rather than purely pharmacological mechanisms. Long-term human safety is not characterised. No human clinical trials published as of 2025.
Given that Dihexa's cognitive effects appear to persist post-washout (structural synaptic remodelling), cycle protocols include mandatory off periods to assess baseline cognition and avoid potential cumulative effects. The HGF/MET pathway promotes neuroplasticity — chronic overstimulation of growth factor receptors warrants caution. No established human protocol; rodent studies used 5-day to 4-week treatment windows.
No published human clinical trial data. Long-term safety profile unknown. HGF/MET receptor signalling promotes cell growth — theoretical concern for individuals with pre-existing malignancies. Not recommended without thorough medical evaluation. Research context only.
Ask anything about Dihexa — mechanisms, dosing protocols, interactions, or research comparisons.
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