What is Dihexa?
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, also coded PNB-0408) is a synthetic, peptide-derived compound developed from angiotensin IV. Its designers modified both ends of Nle-Tyr-Ile, the N-terminal core of the analog Nle¹-angiotensin IV, for metabolic stability and barrier permeability (McCoy et al., 2013). The same laboratory later proposed that Dihexa acts through hepatocyte growth factor (HGF) and its receptor c-Met, but that paper was retracted in 2025, and the 2013 paper carries a 2021 expression of concern. Disguised Alpha supplies it in 5MG capsules for laboratory research use only. Nothing on this page is guidance for use in people.
Dihexa reference data
| Property | Value |
|---|---|
| Name | Dihexa |
| Also called | PNB-0408, ATH-1001, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, Hexanoyl-Tyr-Ile-Ahx-NH2 (PubChem CID 129010512) |
| Structure | N-hexanoyl-L-tyrosyl-L-isoleucine joined to 6-aminohexanoic acid amide: two standard amino acids and a non-standard 6-aminohexanoic acid spacer, linked by amide bonds |
| Compound class | Angiotensin IV-derived peptidomimetic, studied as an HGF/c-Met modulator |
| Molecular formula | C₂₇H₄₄N₄O₅ |
| Molecular weight | 504.7 g/mol |
| PubChem CID | 129010512 |
| Form | Capsules, 5MG per capsule, 60 capsules per bottle (300MG per bottle) |
| Testing | Third-party tested, with the certificate for each lot published on the product page and in the COA portal |
Formula, molecular weight, capsule format and storage are from the Dihexa product page; PubChem CID 129010512 lists the same formula and weight and is the source of the aliases and structure. For quantitative work, use the measured content per capsule on your lot's certificate.
See it beside the other compounds on this site in the peptide molecular weight reference table.
What the research covers
Published work on Dihexa falls into six areas. Each summary below states the model used. The literature is preclinical, and the mechanism needs careful reading because of the retractions described below.
Design and first report
The developers reported that end modifications of the Nle-Tyr-Ile core kept the ability to reverse scopolamine-induced deficits in the Morris water maze and to augment hippocampal synaptogenesis, and that further changes to raise hydrophobicity produced Dihexa, which they described as able to cross the blood-brain barrier and active in scopolamine-treated and aged rats (McCoy et al., 2013). The journal attached an expression of concern to this paper in 2021. Models: rats, plus hippocampal synaptogenesis assays.
The HGF/c-Met mechanism and the 2025 retractions
A 2014 paper from the same laboratory reported that Dihexa binds HGF with high affinity, promotes c-Met phosphorylation at subthreshold HGF concentrations and induces hippocampal synaptogenesis, and that an HGF antagonist blocked its effect in the water maze (Benoist et al., 2014). The journal issued an expression of concern in 2021 and retracted the paper in 2025 (retraction notice, 2025).
A 2012 paper from the group describing the 6-AH family of angiotensin IV analogs as blockers of HGF dimerization was retracted at the same time (Kawas et al., 2012), as was a 2011 paper from the group on mimics of the HGF dimerization domain (Kawas et al., 2011). Later papers still describe Dihexa as an HGF/c-Met modulator, but the retracted work is not evidence. Models in the retracted papers: cell culture, hippocampal neurons and rodent behavior.
Rodent cognition and brain injury models
In APP/PS1 transgenic mice, an Alzheimer's disease model, Dihexa restored spatial learning in the Morris water maze, increased synaptophysin expression, reduced glial activation and pro-inflammatory cytokines, and activated PI3K/AKT signaling; the PI3K inhibitor wortmannin reversed its anti-inflammatory and anti-apoptotic effects (Sun et al., 2021).
In rats given repeated mild closed-head injuries, Dihexa infused into the brain ventricles rescued T-maze working memory at the highest amount tested, and a peptide antagonist of HGF dimerization blocked the effect (Martino et al., 2025). In rats exposed to 3-nitropropionic acid, a model of Huntington's disease-like symptoms, it did not protect against the motor or cognitive deficits (Wells et al., 2024). Models: mouse and rat.
Sensory hair cells in zebrafish
In the larval zebrafish lateral line, whose hair cells resemble those of the mammalian inner ear, Dihexa protected hair cells from neomycin and gentamicin, with optimal protection at 1 micromolar. It did not reduce gentamicin entry, and its protection was attenuated by the HGF antagonist 6-AH and by inhibitors of Akt, TOR and MEK (Uribe et al., 2015). Two of the four authors came from the developing laboratory, and the paper cites the two retracted papers for how 6-AH works and for HGF binding. Model: zebrafish larvae.
Peripheral nerve repair in rats
In a rat sciatic nerve transection and repair model, motor function at 8 to 16 weeks was significantly better when mesenchymal stem cells were given into the gastrocnemius muscle together with either G-CSF or Dihexa (Weiss et al., 2021). The significant motor effect was reported for the combinations, and one author came from the developing laboratory. Model: male Lewis rats.
A growth-factor substitute in stem-cell culture
Two stem-cell groups have used Dihexa as a small-molecule stand-in for HGF. A growth-factor-free protocol paired it with dexamethasone in the final stage of turning human pluripotent stem cells into functional hepatocyte-like cells (Siller et al., 2015).
A later protocol combined vitamin C, Dihexa and forskolin to replace growth factors during hepatic specification, and the resulting cells repopulated injured liver after transplantation into immune-deficient mice (Pan et al., 2022). In both, Dihexa was a culture reagent and was not given to animals. Model: human pluripotent stem cell culture, with a mouse transplant arm in the second study.
Key studies
- McCoy AT, et al. "Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents." J Pharmacol Exp Ther. 2013. PMID 23055539. DOI 10.1124/jpet.112.199497. Rats and synaptogenesis assays: design of Dihexa. Expression of concern, 2021.
- Benoist CC, et al. "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. 2014. PMID 25187433. DOI 10.1124/jpet.114.218735. Retracted by the journal in 2025; listed because it is widely cited, not as evidence.
- Uribe PM, et al. "Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure." Front Cell Neurosci. 2015. PMID 25674052. DOI 10.3389/fncel.2015.00003. Larval zebrafish lateral line.
- Siller R, et al. "Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells." Stem Cell Reports. 2015. PMID 25937370. DOI 10.1016/j.stemcr.2015.04.001. Human pluripotent stem cell culture.
- Sun X, et al. "AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway." Brain Sci. 2021. PMID 34827486. DOI 10.3390/brainsci11111487. APP/PS1 transgenic mice.
- Wells RG, et al. "Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats." J Huntingtons Dis. 2024. PMID 38489193. DOI 10.3233/JHD-231507. Rat model, negative result.
- Martino KA, et al. "Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain Injury." Neurotrauma Rep. 2025. PMID 42825082. DOI 10.1177/2689288X251392851. Rats after repeated mild brain injury.
Handling and storage of Dihexa capsules
General laboratory practice for this material:
- Store the sealed capsules at 15 to 25°C in the original container, away from moisture and direct light (storage guidance on the product page).
- Capsules ship in a sealed bottle or a resealable pouch, depending on the batch; close it fully after each opening and keep it out of humid areas.
- Record the lot number and keep its certificate with your notes. The certificate reports measured content per capsule, which can differ from the 5MG label figure, so use the measured value for quantitative work.
- For identity checks, compare analytical results with the formula C₂₇H₄₄N₄O₅ and molecular weight 504.7 g/mol.
Frequently asked questions
What is Dihexa?
Dihexa is N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, a synthetic, metabolically stabilized angiotensin IV analog (McCoy et al., 2013) studied as a modulator of the HGF/c-Met system.
Is Dihexa a peptide?
It is peptide-derived rather than a natural peptide. The molecule contains two standard amino acids, tyrosine and isoleucine, joined by a peptide bond, plus a 6-aminohexanoic acid spacer ending in an amide, and a hexanoyl cap in place of a free N-terminus. Papers describe it as an angiotensin IV analog (Wells et al., 2024) or as a small-molecule HGF mimetic (Uribe et al., 2015).
What models has Dihexa been studied in?
Rats (memory deficits, repeated mild brain injury, 3-nitropropionic acid toxicity and nerve repair), APP/PS1 transgenic mice, zebrafish hair cells, and human stem cells grown toward liver cells, where it replaced HGF (Siller et al., 2015).
Was the Dihexa HGF/c-Met paper retracted?
Yes. The 2014 paper reporting that Dihexa binds HGF and that its effects depend on c-Met was retracted by its journal in 2025 (Benoist et al., 2014), and the 2013 paper that introduced Dihexa carries a 2021 expression of concern (McCoy et al., 2013). An independent rat study has since reported that an HGF dimerization antagonist blocked a Dihexa effect (Martino et al., 2025), but the mechanism remains a hypothesis.
Has Dihexa been tested in people?
Not as Dihexa itself in any trial indexed in PubMed, and it is not an approved drug. A related compound, fosgonimeton, which PubChem records (CID 156596375) as the same backbone carrying a phosphate group on the tyrosine side chain and which its developers describe as a prodrug (Johnston et al., 2023), was well tolerated in a phase 1 trial (Hua et al., 2022) and did not meet its primary or secondary endpoints in a phase 2/3 Alzheimer's disease trial (Porsteinsson et al., 2025). Those results describe fosgonimeton, not research-grade Dihexa.
How should Dihexa capsules be stored?
Keep them sealed in the original container at 15 to 25°C, away from moisture and direct light, as listed on the product page.
Where can researchers buy Dihexa?
Disguised Alpha sells Dihexa for laboratory research as 5MG capsules, 60 per bottle, third-party tested with the certificate published on the product page: Dihexa. An aerosol format is listed separately as Dihexa Aerosol Spray.
Related compounds and guides
- Dihexa Aerosol Spray
- Energize (Dihexa / Semax / Selank Aerosol Spray)
- Semax research guide
- Selank research guide
- Semax vs Selank: research comparison
- COA portal: every published certificate, by lot
This product is for research use only. It has not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.