Dihexa
Also known as N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
A metabolically stabilized small peptide analogue derived from angiotensin IV. It is studied in rodent models for synaptogenic and procognitive effects, though key mechanistic papers carry an expression of concern or have been retracted.
Preclinical research
Size
1 option- Catalog no.
- DX10
- Specification
- 10mg*10vials
- Per kit
- 10 vials
For laboratory research use only. Not for human or animal consumption. Buyers must be 21 or older.
Overview
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) was developed at Washington State University from Nle-Tyr-Ile, the three N-terminal residues of the angiotensin IV analogue norleucine1-angiotensin IV. Terminal modifications were added to resist enzymatic breakdown and to cross the blood-brain barrier. Rodent studies reported reversal of scopolamine-induced and age-related memory deficits and increased hippocampal synapse formation. The literature needs careful reading: the 2013 paper describing Dihexa received an expression of concern in 2021, and a 2014 paper proposing its HGF/c-Met mechanism was retracted in 2025. No human trials have been published.
Class: Angiotensin IV-derived peptidomimetic
Mechanism of action
How the compound acts, as described in the literature.
Built on Nle-Tyr-Ile, the minimal procognitive sequence of norleucine1-angiotensin IV, with N- and C-terminal changes that increased hydrophobicity and metabolic stability.
Proposed to bind hepatocyte growth factor (HGF) and enhance c-Met receptor activation; the principal paper supporting this mechanism (Benoist 2014) was retracted in 2025, so the mechanism is not firmly established.
Rat studies reported increased hippocampal synaptogenesis (McCoy 2013); that paper carries a 2021 expression of concern from the journal.
In APP/PS1 mice, reported effects on memory, neuron counts, and glial activation were reversed by the PI3K inhibitor wortmannin, implicating PI3K/AKT signaling (Sun 2021).
Published research
Selected studies, each linked to its PubMed record. Summaries describe what the studies reported.
2013
Rodent study
PMID 23055539Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.
McCoy AT, et al. · J Pharmacol Exp Ther
Dihexa reversed scopolamine-induced and age-related deficits in rat water maze performance and showed marked synaptogenic activity. The journal issued an expression of concern for this paper in 2021.
2021
Mouse study
PMID 34827486AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.
Sun X, et al. · Brain Sci
In APP/PS1 mice, Dihexa improved water maze performance, preserved neurons and synaptic protein, and reduced glial activation and inflammation; the PI3K inhibitor wortmannin reversed these effects.
2015
Review
PMID 25455861The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.
Wright JW, et al. · Prog Neurobiol
Reviews the brain angiotensin IV/AT4 receptor system and the development of stabilized angiotensin IV analogues, including Dihexa, in models of Alzheimer's and Parkinson's disease; notes the AT4 receptor's identity is debated.
Evidence & safety
What the research does not show, and the adverse events and regulatory status it reports.
Evidence is limited to rodent studies; the 2013 paper introducing Dihexa carries a 2021 expression of concern, and the 2014 paper proposing its HGF/c-Met mechanism was retracted in 2025. No human safety or pharmacokinetic data have been published. Its proposed target pathway, HGF/c-Met, also drives growth and invasion in many cancers, a theoretical risk that has not been studied.
Specifications
All sizes, exactly as catalogued.
| Catalog no. | Product | Specification | Vials per kit |
|---|---|---|---|
| DX10 | Dihexa | 10mg*10vials | 10 |
For laboratory research use only. Not for human or animal consumption. Not intended to diagnose, treat, cure or prevent any disease. Research summaries are provided for educational purposes and do not describe this product’s use.