Dihexa — Complete Research Guide (2026)
Last updated 2026-06-25
TL;DR
An angiotensin-IV-derived peptide studied in preclinical models for synaptogenesis and cognition; no human approval.
What is Dihexa?
Dihexa (N-hexanoic-Tyr-Ile-(6)aminohexanoic amide; also called PNB-0408) is a metabolically stabilized compound derived from angiotensin IV, studied for effects on synapse formation and cognition.
It is an unapproved investigational research compound with no marketing authorization from the FDA, EMA, or any other regulator.
The entire published evidence base is preclinical (cell culture and rodent models); no human clinical trials have been reported.
How does Dihexa work?
Dihexa is reported to promote synaptogenesis and procognitive effects through activation of the hepatocyte growth factor (HGF)/c-Met receptor system.
In an Alzheimer's mouse model its cognitive effects were linked to PI3K/AKT signaling. [INFOGRAPHIC: Dihexa HGF/c-Met synaptogenesis]
What does the research say about Dihexa?
- As a metabolically stabilized angiotensin IV analog, dihexa improved measures of cognition in preclinical antidementia models. [1]
- Its procognitive and synapse-forming effects in preclinical work depend on activation of the HGF/c-Met system. [2]
- In an APP/PS1 Alzheimer's mouse model, dihexa rescued cognitive impairment and recovered memory via PI3K/AKT signaling. [3]
Clinical research & studies
The references below are the primary sources cited throughout this guide. Each links directly to PubMed or the regulator. Where evidence is preclinical (animal or in-vitro), that is stated rather than implied.
- [1] Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — McCoy AT et al., J Pharmacol Exp Ther 2013. (animal / in-vitro)
- [2] The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system — Benoist CC et al., J Pharmacol Exp Ther 2014. (in-vitro / animal)
- [3] 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 Sci 2021. (animal)
- [4] Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats — Wells RG et al., J Huntingtons Dis 2024. (animal)
- [5] The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases — Wright JW et al., Prog Neurobiol 2015. (review)
- [6] Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies — Ho JK et al., Neurosci Biobehav Rev 2018. (review)
Dosing context
No human dose has been established; published work uses rodent dosing that cannot be translated into human protocols.
Any human dosing figures circulating online are anecdotal and unsupported by clinical research.
Side effects & safety profile
There are no human safety trials of dihexa; its safety, tolerability, and toxicology in people are unknown.
Because it is a potent promoter of growth-factor (HGF/c-Met) signaling, theoretical concerns such as unwanted cell proliferation have not been resolved in human studies.
It is strictly an investigational research chemical and is not approved for any human use.
Stacking & combinations
There are no human data on combining dihexa with other compounds, and any such stacking is unstudied speculation.
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Frequently asked questions
Dihexa (PNB-0408) is a metabolically stabilized compound derived from angiotensin IV, studied preclinically for effects on synapse formation and cognition.
References
- [1] Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — McCoy AT et al., J Pharmacol Exp Ther 2013. PMID: 23055539. View sourceStudy: animal / in-vitroIntroduced dihexa as a metabolically stabilized angiotensin IV analog with procognitive activity in rodent models.
- [2] The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system — Benoist CC et al., J Pharmacol Exp Ther 2014. PMID: 25187433. View sourceStudy: in-vitro / animalShowed dihexa's synaptogenic and procognitive effects require the HGF/c-Met system.
- [3] 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 Sci 2021. PMID: 34827486. View sourceStudy: animalDihexa improved cognition and memory in an APP/PS1 Alzheimer's mouse model through PI3K/AKT signaling.
- [4] Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats — Wells RG et al., J Huntingtons Dis 2024. PMID: 38489193. View sourceStudy: animalAn angiotensin IV analog (dihexa) reduced Huntington's-disease-like symptoms in a rat model.
- [5] The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases — Wright JW et al., Prog Neurobiol 2015. PMID: 25455861. View sourceStudy: reviewReviews the rationale and preclinical development of angiotensin IV analogs including dihexa for neurodegenerative disease.
- [6] Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies — Ho JK et al., Neurosci Biobehav Rev 2018. PMID: 29733881. View sourceStudy: reviewSystematic review of experimental (preclinical) studies reporting cognitive benefits of angiotensin IV-related peptides.