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Research details
Dihexa — research data
Research-literature reference data, NOT patient instructions. Not for human use. Consult a licensed clinician for any human application.
Overview
About Dihexa
Mechanism of action
HGF/MET system potentiator; derived from angiotensin IV; binds hepatocyte growth factor (HGF) and prevents its degradation; activates MET receptor; promotes synaptogenesis, dendritic spine density, and neuroplasticity; ~7 orders of magnitude more potent than BDNF per unit.
Safety profile
Limited human data. Potential: overstimulation, anxiety, insomnia at high doses. Theoretical cancer concern (HGF/MET pathway implicated in tumor growth — use with caution in cancer history). · Acts via c-Met activation — a tumor-growth pathway — giving a real oncogenicity concern; no long-term or human safety data; no human trials. Generally avoided with any cancer history.
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Research
Studies & key findings
- Dihexa is an orally active, blood-brain-barrier-permeable angiotensin IV analogue that potentiates hepatocyte growth factor (HGF) signaling at the c-Met receptor; the original 2014 JPET paper (PMID 25187433) reported it induced hippocampal spinogenesis and synaptogenesis orders of magnitude more potently than BDNF — however, this paper was formally retracted in April 2025 (PMID 40312093) due to data integrity concerns, and its primary findings should not be cited as established.
- A 2021 Brain Sciences study independent of the retracted group found that Dihexa treatment improved spatial learning and memory in APP/PS1 Alzheimer's model mice, reduced neuroinflammatory markers, and restored neuronal populations; the beneficial effects were blocked by PI3K/AKT pathway inhibitors, identifying this axis as the operative downstream mechanism.