What it is
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is an analog of angiotensin IV, meaning a chemically modified version of that peptide. It is studied for its ability to promote synapse formation, the growth of new connections between neurons, and has been investigated in preclinical models of neurodegeneration.
In the PeptidesAI encyclopedia it is categorized under cognitive.
How it's thought to work
Dihexa is proposed to enhance signaling through hepatocyte growth factor (HGF) and its receptor c-Met, driving synaptogenesis, the formation of new synapses. That mechanism was proposed in a 2014 paper that the journal retracted in 2025, so it is currently unconfirmed.
What the research says
Preclinical studies originating at Washington State University reported effects on synapse formation and on memory in rodent models. A 2014 paper from that group proposing the HGF/c-Met mechanism was retracted by the journal in 2025, and the group's 2013 paper on dihexa carries an editorial expression of concern issued in 2021.
An independent 2021 study in a mouse model of Alzheimer's disease reported that dihexa improved spatial learning and lowered inflammatory cytokine levels. There are no human clinical trials, and dihexa is not FDA-approved.
Reported side effects
Human safety data is very limited. A theoretical concern raised for dihexa is its growth-factor signaling mechanism together with unknown long-term effects.
Form
Dihexa is studied as an orally active compound in powder or capsule form, so it is not reconstituted like an injectable peptide.
Important notes
Dihexa has minimal human safety data and is not FDA-approved. The key mechanism paper behind it has been retracted, and the evidence base is almost entirely animal and laboratory work.
Sources
- Retraction notice to "The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System" [J Pharmacol Exp Ther 351 (2014) 390-402].. Benoist CC et al. Journal of Pharmacology and Experimental Therapeutics, 2025. Announcement
- Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.. McCoy AT et al. Journal of Pharmacology and Experimental Therapeutics, 2013. Preclinical
- AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.. Sun X et al. Brain Sciences, 2021. Preclinical
Frequently asked questions
These questions cover the same ground as the sections above, in a shorter format.
What is dihexa?
An angiotensin IV analog studied in rodents for promoting synapse formation. It has not been tested in human clinical trials.
How is dihexa thought to work?
It is proposed to enhance HGF/c-Met signaling to drive synaptogenesis, but the 2014 paper proposing that mechanism was retracted in 2025, so it is unconfirmed.
What does the research on dihexa say?
Preclinical studies in rodents report effects on synapse formation and memory. Key papers from the originating group have been retracted or carry an expression of concern, and there are no human trials.
What are the reported side effects of dihexa?
Human safety data is very limited; the long-term effects are unknown.
The full entry, plus the calculator
The PeptidesAI app has the complete encyclopedia entry for Dihexa — one of 70 compounds covered — plus the reconstitution calculator, a dose log and reminders. Free to download on iPhone.
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